You searched for subject:(HCV).
Showing records 1 – 30 of
392 total matches.
◁ [1] [2] [3] [4] [5] … [14] ▶
1.
Simeon, Rudo Lyndon.
Selecting a path against Hepatitis C Virus.
Degree: 2013, Texas Digital Library
URL: http://hdl.handle.net/1969; 
http://hdl.handle.net/2249.1/66834
► Hepatitis C virus (HCV) currently affects ~5% of the world???s population and has relatively limited treatment options for infected patients. Genetic suppressor elements (GSE) derived…
(more)
▼ Hepatitis C virus (
HCV) currently affects ~5% of the world???s population and has relatively limited treatment options for infected patients. Genetic suppressor elements (GSE) derived from a gene or genome of interest can act as transdominant inhibitors of a particular biology function presumably by binding to and blocking an essential interaction surface for protein activity. Taking advantage of hepatoma cell line n4mBid, that supports all stages of the
HCV life cycle and strongly report
HCV infection by a cell-death phenotype, we developed an iterative selection/enrichment strategy for the identification of GSE against
HCV. Using this strategy, a library expressing random fragments of the
HCV genome was screened for sequences able to suppress
HCV infection. A 244 amino acid gene fragment, B1, was strongly enriched after 5 rounds of selection. B1 has a very high net positive charge of 43 at neutral pH and a high charge-to-mass (kDa) ratio of 1.5. We show that B1 expression specifically inhibits
HCV replication, apparently due to its high positive charge. We also show that recombinant positively charged proteins can inhibit
HCV infection, when supplied in vitro.In addition, eGFP-fused B1 potently penetrates both adherent and suspension cells with >80% of cells taking up the protein. Importantly, we show that B1 not only facilitates cellular uptake, but allows protein cargo to reach sites of biological relevance. B1 also delivers non-covalently conjugated RNA and DNA across the cell membrane to cytosolic and nuclear sites, with efficiency comparable to commercially available cationic lipid reagents. Our data suggest that B1 utilizes cell-surface glycans and multiple competing endocytic pathways to enter and traffic through cells.During a separate screening carried out in our lab, we identified a TACR3 inhibitor SB 222200 that had significant
HCV activity. We go on to show that both TACR1 and TACR3 receptors are expressed in the
HCV-permissive Huh 7.5 cell line. We also show that both TACR1 and TACR3 inhibitors significantly inhibit
HCV infection. These results point to the potential for TACR1 antagonists in treating patients infected with both
HCV and HIV.
Advisors/Committee Members: Chen, Zhilei (advisor).
Subjects/Keywords: HCV
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Simeon, R. L. (2013). Selecting a path against Hepatitis C Virus. (Thesis). Texas Digital Library. Retrieved from http://hdl.handle.net/1969; http://hdl.handle.net/2249.1/66834
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Simeon, Rudo Lyndon. “Selecting a path against Hepatitis C Virus.” 2013. Thesis, Texas Digital Library. Accessed March 04, 2021.
http://hdl.handle.net/1969; http://hdl.handle.net/2249.1/66834.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Simeon, Rudo Lyndon. “Selecting a path against Hepatitis C Virus.” 2013. Web. 04 Mar 2021.
Vancouver:
Simeon RL. Selecting a path against Hepatitis C Virus. [Internet] [Thesis]. Texas Digital Library; 2013. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1969; http://hdl.handle.net/2249.1/66834.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Simeon RL. Selecting a path against Hepatitis C Virus. [Thesis]. Texas Digital Library; 2013. Available from: http://hdl.handle.net/1969; http://hdl.handle.net/2249.1/66834
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Queens University
2.
Huang, George.
Modeling the Impact of Needle Exchange Programs Accounting for both HIV and HCV Infections and HIV/CV Co-Infections
.
Degree: Community Health and Epidemiology, 2014, Queens University
URL: http://hdl.handle.net/1974/12155
► Purpose: The aim of this study is to model the impact of needle exchange interventions on human immunodeficiency virus (HIV) and hepatitis C virus (HCV).…
(more)
▼ Purpose: The aim of this study is to model the impact of needle exchange interventions on human immunodeficiency virus (HIV) and hepatitis C virus (HCV).
Methods: In order to model the impact of needle exchange interventions, behavioural effects (sexual and drug use) were translated into estimates of the number of HIV and HCV cases averted by the programs through a mathematical model. Behavioural effects data on 63 clients had been collected previously by two Health Units in Ontario. The secondary data were analyzed to estimate the number of HIV and HCV cases averted while accounting for co-infection. A Bernoulli process model was used to estimate the number of averted cases for the condom distribution and counselling aspects of the needle exchange intervention. A modification of the Bernoulli process model was used for needle exchange interventions to account for drug use behaviours. Furthermore, this model estimated the number of cases averted while also accounting for the clients’ partner’s co-infection status. Once the number of HIV and HCV cases averted was determined, a cost analysis was conducted to estimate the net medical savings of the interventions. Costs were converted to 2011 Canadian dollars.
Results: Of the 63 clients, 21.40 HIV and 5.18 HCV cases were directly averted by the needle exchange intervention when HIV/HCV co-infection status of the partner was not taken into account. When the clients’ partners’ co-infection status was taken into account, lesser numbers were directly averted by the needle exchange intervention. The discounted medical savings averted were 6,950,028 and 6,741,331 when co-infection was and was not accounted for, respectively, for the 63 individuals.
Conclusion: The study demonstrated a different modeling method to account for HIV and HCV cases averted in the context of needle exchange. This study provides a foundation for future large scale cost-effectiveness studies.
Subjects/Keywords: HCV
;
HIV
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Huang, G. (2014). Modeling the Impact of Needle Exchange Programs Accounting for both HIV and HCV Infections and HIV/CV Co-Infections
. (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/12155
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Huang, George. “Modeling the Impact of Needle Exchange Programs Accounting for both HIV and HCV Infections and HIV/CV Co-Infections
.” 2014. Thesis, Queens University. Accessed March 04, 2021.
http://hdl.handle.net/1974/12155.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Huang, George. “Modeling the Impact of Needle Exchange Programs Accounting for both HIV and HCV Infections and HIV/CV Co-Infections
.” 2014. Web. 04 Mar 2021.
Vancouver:
Huang G. Modeling the Impact of Needle Exchange Programs Accounting for both HIV and HCV Infections and HIV/CV Co-Infections
. [Internet] [Thesis]. Queens University; 2014. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1974/12155.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Huang G. Modeling the Impact of Needle Exchange Programs Accounting for both HIV and HCV Infections and HIV/CV Co-Infections
. [Thesis]. Queens University; 2014. Available from: http://hdl.handle.net/1974/12155
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Boston University
3.
Freiman, J. Morgan.
Evidence toward a novel approach to hepatitis C virus testing in resource-limited settings.
Degree: MS, Epidemiology, 2018, Boston University
URL: http://hdl.handle.net/2144/27854
► RATIONALE: A low cost point of care test (POCT) to diagnose hepatitis C virus (HCV) viremia could be a critical step toward HCV elimination. The…
(more)
▼ RATIONALE: A low cost point of care test (POCT) to diagnose hepatitis C virus (
HCV) viremia could be a critical step toward
HCV elimination. The aim of this study is to inform the limit of detection (LOD) for an affordable POC test.
METHODS: This study analyzed a convenience sample of cross-sectional
HCV testing data from reference laboratories and clinical research studies in 9 countries. Participants of all ages with quantified
HCV viremia were included. We analyzed the distribution of
HCV viral load for the first detectable
HCV RNA available, and derived the clinical sensitivity for a POCT with an LOD of 3 log IU/mL. Bivariate and multivariate analyses were then performed to identify demographic and clinical characteristics associated with low-level viremia (< 3 log IU/mL).
RESULTS: The dataset included 53,295 participants from Cambodia, Canada, Cameroon, Georgia, Indonesia, Malaysia, Pakistan, Thailand, and Vietnam. Log
HCV RNA was normally distributed, and ≥ 3 log IU/mL corresponded with clinical sensitivity of 98%. Neither HIV co-infection nor cirrhosis were significantly associated with low-level viremia, whereas bivariate analyses showed increased odds of 2.47 (95% CI 2.04, 2.99) for low-level
HCV RNA among those ≤ 30 years old compared to those > 30, and an OR of 1.17 (1.02, 1.34) among females compared to males. Stepwise multivariate regression found no significant confounding.
CONCLUSION: In this global dataset, a POCT with a LOD of 3 log IU/mL would identify 98% of chronic
HCV infections. The increase OR among those ≤ 30 years old year olds is likely explained by a greater frequency among younger persons of recent infection, where fluctuating viremia is well described. A POCT for
HCV that could identify persons with 3 log IU/mL or greater would likely facilitate affordable product development and expand the reach of
HCV testing in resource-limited settings.
Advisors/Committee Members: Horsburgh, C. Robert (advisor).
Subjects/Keywords: Epidemiology; HCV
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Freiman, J. M. (2018). Evidence toward a novel approach to hepatitis C virus testing in resource-limited settings. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/27854
Chicago Manual of Style (16th Edition):
Freiman, J Morgan. “Evidence toward a novel approach to hepatitis C virus testing in resource-limited settings.” 2018. Masters Thesis, Boston University. Accessed March 04, 2021.
http://hdl.handle.net/2144/27854.
MLA Handbook (7th Edition):
Freiman, J Morgan. “Evidence toward a novel approach to hepatitis C virus testing in resource-limited settings.” 2018. Web. 04 Mar 2021.
Vancouver:
Freiman JM. Evidence toward a novel approach to hepatitis C virus testing in resource-limited settings. [Internet] [Masters thesis]. Boston University; 2018. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2144/27854.
Council of Science Editors:
Freiman JM. Evidence toward a novel approach to hepatitis C virus testing in resource-limited settings. [Masters Thesis]. Boston University; 2018. Available from: http://hdl.handle.net/2144/27854
University of New South Wales
4.
Sugden, Peter Burnet.
Determinants of protection against hepatitis C virus infection in highly exposed, uninfected individuals.
Degree: Medical Sciences, 2014, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/53638
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12333/SOURCE02?view=true
► Introduction: Individuals infected with hepatitis C virus (HCV) have two recognised outcomes of infection, clearance or persistence. Individuals who clear remain susceptible to re-infection. Some…
(more)
▼ Introduction: Individuals infected with hepatitis C virus (
HCV) have two recognised outcomes of infection, clearance or persistence. Individuals who clear remain susceptible to re-infection. Some high-risk individuals have been found to have
HCV-specific immune responses in the absence of apparent infection, possibly indicating an exposed-but-uninfected (EU) phenotype, with protective immunity. This thesis sought to better understand this phenotype by examining: occult infection (with low level virus undetected by standard assays), the characteristics of potentially protective cellular immunity, and identification of potential genetic factors associated with EU status. Subjects and Methods: For occult infection, a two centre, masked, case-control study (n=35) and a longitudinal study (n=32) were undertaken using ultrasensitive nested PCR. For the protective immunity study, a nested case-control series with incident cases (n=28) and matched EU subjects (n=28) was analysed for natural killer cell (NK) phenotypes and
HCV-specific CD4 and CD8 T cell responses. For the genetics study, DNA (n=210 subjects designated by varied risk of
HCV infection) were genotyped for polymorphisms associated with clearance. To quantify risk, a composite index was derived from longitudinally collected risk behaviour data predicting incident infection in a prospective cohort of injecting drug user, prison inmates. Results: Two EU subjects in the first study (10%) and one in the second study (3%) were found to have consistently detectable
HCV RNA. The numbers of activated (CD69+) NK cells in the mature CD56LowCD16+ subset, and cytotoxic (NKp30+) cells in the CD56HighCD16+ subset were higher in the EU subjects (p=0.040, p=0.038 respectively). EU subjects had higher frequencies of interferon (IFN)-γ producing NK cells, and lower frequencies of CD107a expression (p=0.003, p=0.015 respectively). No other factor differed. The risk index was strongly associated with incident
HCV infection (p<0.0001). There were no significant differences in frequencies of the genetic markers. Conclusion: Occult infection occurs rarely in apparently uninfected subjects. NK cell activation is associated with likely protection against
HCV infection. Genetic determinants of resistance to
HCV infection remain to be identified. Further studies to confirm NK cell-mediated protection and to understand the mechanisms are needed.
Advisors/Committee Members: Lloyd, Andrew, Medical Sciences, Faculty of Medicine, UNSW, Cameron, Barbara, Medical Sciences, Faculty of Medicine, UNSW.
Subjects/Keywords: HCV; Immunology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sugden, P. B. (2014). Determinants of protection against hepatitis C virus infection in highly exposed, uninfected individuals. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/53638 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12333/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Sugden, Peter Burnet. “Determinants of protection against hepatitis C virus infection in highly exposed, uninfected individuals.” 2014. Doctoral Dissertation, University of New South Wales. Accessed March 04, 2021.
http://handle.unsw.edu.au/1959.4/53638 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12333/SOURCE02?view=true.
MLA Handbook (7th Edition):
Sugden, Peter Burnet. “Determinants of protection against hepatitis C virus infection in highly exposed, uninfected individuals.” 2014. Web. 04 Mar 2021.
Vancouver:
Sugden PB. Determinants of protection against hepatitis C virus infection in highly exposed, uninfected individuals. [Internet] [Doctoral dissertation]. University of New South Wales; 2014. [cited 2021 Mar 04].
Available from: http://handle.unsw.edu.au/1959.4/53638 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12333/SOURCE02?view=true.
Council of Science Editors:
Sugden PB. Determinants of protection against hepatitis C virus infection in highly exposed, uninfected individuals. [Doctoral Dissertation]. University of New South Wales; 2014. Available from: http://handle.unsw.edu.au/1959.4/53638 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12333/SOURCE02?view=true
University of Saskatchewan
5.
Wu, Qi.
MOLECULAR PATHOGENESIS OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS INFECTIONS.
Degree: 2017, University of Saskatchewan
URL: http://hdl.handle.net/10388/7984
► Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections cause a wide range of liver diseases including hepatocellular carcinoma (HCC) worldwide. Because these two…
(more)
▼ Hepatitis B virus (HBV) and hepatitis C virus (
HCV) infections cause a wide range of liver diseases including hepatocellular carcinoma (HCC) worldwide. Because these two viruses have the same modes of transmission, HBV
HCV co-infections are found in approximately 7 to 20 million people globally. HBV
HCV co-infections are associated with more severe liver diseases and higher risk of HCC. Previous studies have established that HBV and
HCV mono-infection can cause hepatic steatosis, and steatosis is a confirmed risk factor for HCC. However, whether and how HBV
HCV co-infections synergistically increase the risk of HCC development through modulating lipid metabolism is not well understood.
PTEN is a phosphatase which contains both lipid and protein phosphatase activities. PTEN acts as a tumor suppressor by down-regulating the phosphoinositide-3-kinase (PI3K)/Akt/ sterol regulatory element-binding protein (SREBP) signaling pathway. It has been reported that PTEN is frequently mutated or deleted in tumors including HCC. PTEN-Long, a longer isoform of PTEN, which is able to be exported into the extracellular compartments, enter neighboring cells, and induce signaling events in recipient cells. Both HBV and
HCV infections can inhibit PTEN and activate SREBP. However, how regulation of PTEN/SREBP pathway affects HBV and
HCV infections is not fully understood. Therefore, the effect of the PTEN/SREBP pathway on HBV and/or
HCV infections is worthy to study.
In this study, we showed that both HBV X protein (HBx) and
HCV core protein regulate PTEN/SREBP pathway. We established that HBx activates SREBP-1a and SREBP-1c through different mechanisms. This process is involved in up-regulating of HBV enhancer I or HBV enhancer II. We demonstrated multiple mechanisms of how HBx regulates HBV replication. We also showed that
HCV core interacts with PTEN and PTEN-Long which is involved in regulating of
HCV life cycle. In an HBV
HCV co-infection cellular model, HBx and
HCV core have similar regulatory effects on the PTEN/SREBP pathway as in mono-infections. However, PTEN and SREBP differentially regulate HBV and
HCV replication in HBV
HCV co-infection.
Advisors/Committee Members: Liu, Qiang, Hill, Janet, Chelico, Linda, Liu, Lixin, Anderson, Deborah.
Subjects/Keywords: HBV; HCV; HBx; HCV core; PTEN; SREBP
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wu, Q. (2017). MOLECULAR PATHOGENESIS OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS INFECTIONS. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/7984
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wu, Qi. “MOLECULAR PATHOGENESIS OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS INFECTIONS.” 2017. Thesis, University of Saskatchewan. Accessed March 04, 2021.
http://hdl.handle.net/10388/7984.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wu, Qi. “MOLECULAR PATHOGENESIS OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS INFECTIONS.” 2017. Web. 04 Mar 2021.
Vancouver:
Wu Q. MOLECULAR PATHOGENESIS OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS INFECTIONS. [Internet] [Thesis]. University of Saskatchewan; 2017. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10388/7984.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wu Q. MOLECULAR PATHOGENESIS OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS INFECTIONS. [Thesis]. University of Saskatchewan; 2017. Available from: http://hdl.handle.net/10388/7984
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Saskatchewan
6.
Kandangwa, Mangyung Limbu 1993-.
Investigating the Hepatitis C Virus (HCV) RNA Translation Modulation by Non-Structural Protein 5A (NS5A).
Degree: 2016, University of Saskatchewan
URL: http://hdl.handle.net/10388/12539
► Hepatitis C virus (HCV) non-structural protein NS5A is a multifunctional protein and despite lacking enzymatic activity has critical roles in viral replication and assembly. The…
(more)
▼ Hepatitis C virus (
HCV) non-structural protein NS5A is a multifunctional protein and despite lacking enzymatic activity has critical roles in viral replication and assembly. The role of NS5A in
HCV RNA translation has not been well studied. In an attempt to better understand the role of
HCV NS5A in RNA translation, our previous work showed that
HCV-1b NS5A downregulates viral RNA translation by binding to the poly(U/UC) region in the 3’UTR. All three domains are capable of individually downregulating translation, albeit with a lesser effect than the full-length wild-type NS5A.
There are multiple
HCV genotypes and NS5A from different genotypes may or may not carry out the same function. Therefore, to determine whether the role of NS5A is conserved in other genotypes, we studied the effect of
HCV-2a NS5A on monocistronic
HCV-2a RNA reporters and replication defective genomic RNA with or without poly(U/UC) region at the 3’UTR. We found that although
HCV-2a NS5A also downregulates viral translation, it does not require the poly(U/UC) region in 3’UTR. The translation downregulation by
HCV-2a NS5A was predominantly mediated by domain I. Our results elucidated that
HCV-2a NS5A modulates viral translation through a mechanism different from
HCV-1b NS5A.
NS5A is a phospho-protein and exists as hypo- and hyper-phosphorylated NS5A. The hyperphosphorylation of NS5A is mediated through the phosphorylation of the conserved serine residues cluster in the low complexity sequence LCS I. The serine residues are S222, S225, S229, S232, S235 and S238. Phosphorylation on these serine residues has been found to be important for
HCV replication and viral assembly. To further understand the significance of NS5A hyperphosphorylation on
HCV life cycle, we investigated the role of
HCV-1b NS5A hyperphosphorylation on translation by analyzing the effects of phospho-ablative and phospho-mimetic mutants of the six serine residues on
HCV-1b genomic RNA translation. We showed that phosphorylation of S222, S225, S235 is not involved in translation downregulation by NS5A. In contrast, alanine mutations at S229 or S238 can no longer downregulate translation, whereas S229D or S238D mutations have no effect. Interestingly, S232D, but not S232A, abrogates translation downregulation by NS5A.
NS5A exists as a dimer and its dimerization is important for regulating its function. Therefore, we studied the effect of phospho-mutants of S229, S232, and S238 on dimerization in a protein-protein interaction assay and showed that phospho-mimetic S229D or S238D mutations enhance NS5A dimerization, whereas the phospho-ablative mutations of them have no effect. In contrast, neither phospho-ablative nor phospho-mimetic mutations of S232 affect dimerization. In conclusion, these results indicated that phosphorylation of NS5A at S229, S232, and S238 is involved in viral translation regulation and NS5A dimerization.
In summary, these findings suggest that NS5A downregulates the translation of
HCV RNA however, the mechanism may differ within the genotypes. In addition,…
Advisors/Committee Members: Liu, Qiang, Tikoo, Suresh, Falzarano, Darryl, Luo , Yu.
Subjects/Keywords: HCV NS5A; HCV RNA translation; NS5A hyperphophorylation
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kandangwa, M. L. 1. (2016). Investigating the Hepatitis C Virus (HCV) RNA Translation Modulation by Non-Structural Protein 5A (NS5A). (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/12539
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kandangwa, Mangyung Limbu 1993-. “Investigating the Hepatitis C Virus (HCV) RNA Translation Modulation by Non-Structural Protein 5A (NS5A).” 2016. Thesis, University of Saskatchewan. Accessed March 04, 2021.
http://hdl.handle.net/10388/12539.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kandangwa, Mangyung Limbu 1993-. “Investigating the Hepatitis C Virus (HCV) RNA Translation Modulation by Non-Structural Protein 5A (NS5A).” 2016. Web. 04 Mar 2021.
Vancouver:
Kandangwa ML1. Investigating the Hepatitis C Virus (HCV) RNA Translation Modulation by Non-Structural Protein 5A (NS5A). [Internet] [Thesis]. University of Saskatchewan; 2016. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10388/12539.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kandangwa ML1. Investigating the Hepatitis C Virus (HCV) RNA Translation Modulation by Non-Structural Protein 5A (NS5A). [Thesis]. University of Saskatchewan; 2016. Available from: http://hdl.handle.net/10388/12539
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
7.
COSTA, Joanne Elizabeth Ferraz da.
Ocorrência de marcadores dos vírus da hepatite B e C e de infecção oculta pelo vírus da hepatite B em pacientes com hanseníase na Paraíba
.
Degree: 2017, Universidade Federal de Pernambuco
URL: https://repositorio.ufpe.br/handle/123456789/24984
► Estudos têm reportado maiores prevalências de marcadores sorológicos do vírus da hepatite B (HBV) e da hepatite C (HCV) em pacientes hansênicos e sua associação…
(more)
▼ Estudos têm reportado maiores prevalências de marcadores sorológicos do vírus da hepatite B (HBV) e da hepatite C (
HCV) em pacientes hansênicos e sua associação com os episódios reacionais. Por outro lado, a deficiência imune apresentada por esses pacientes pode predispor à ocorrência de infecção oculta pelo HBV. O objetivo desta pesquisa foi determinar a prevalência e fatores de risco para os marcadores sorológicos do HBV e do
HCV e para a infecção oculta pelo HBV em pacientes com hanseníase. Foi realizado estudo transversal no período de fevereiro de 2015 a janeiro de 2016 em pacientes de Centro de Referência em hanseníase na Paraíba, que após assinatura de termo de consentimento livre e esclarecido foram submetidos à entrevista e coleta de amostras sanguíneas. Os testes sorológicos (ELISA) foram realizados no Setor de Virologia do Laboratório de Imunopatologia Keizo Asami (LIKA) da Universidade Federal de Pernambuco (UFPE). Amostras de plasma foram encaminhadas ao Laboratório Central de Saúde Pública do Estado da Paraíba para estudo molecular (HBV DNA;
HCV RNA) por PCR em tempo real. Foram incluídos 403 pacientes no estudo sorológico e 114 pacientes na pesquisa da infecção oculta (HBV DNA). Foi observada frequência de anti-HBc de 14,1% (57/403), de HBsAg 0% (0/403), de anti-HBs isolado 14,1% (57/403), de anti-
HCV 0,5% (2/403) e de infecção oculta por HBV 5,3% (6/114). Quanto aos fatores de risco, identificou-se associação do anti-HBc com ter trabalhado na área de saúde e com um menor número de anos de estudo (até nove anos). Não foi observada associação do anti-HBc ou anti-
HCV com episódios reacionais, porém identificou-se associação da infecção oculta pelo HBV com história de episódio reacional tipo 2. Assim, as prevalências dos marcadores do HBV e do
HCV em hansênicos de Centro de Referência na região Nordeste foram semelhantes às da população geral da mesma região, sugerindo que estes pacientes não apresentam propensão para a infecção crônica por esses vírus. Este foi o primeiro estudo no Brasil sobre a infecção oculta pelo HBV em hansênicos, demonstrando que a pesquisa do HBV DNA deve ser considerada durante o acompanhamento do paciente com hanseníase, tendo em vista a possibilidade de ocorrência de infecção oculta nesses indivíduos. Estudos prospectivos que incluam maior número de pacientes poderão contribuir para uma melhor compreensão da influência da infecção oculta na evolução da hanseníase e em seu tratamento.
Advisors/Committee Members: COÊLHO, Maria Rosângela Cunha Duarte (advisor), http://lattes.cnpq.br/7133083621997139 (advisor).
Subjects/Keywords: HBV;
HCV;
Hanseníase
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
COSTA, J. E. F. d. (2017). Ocorrência de marcadores dos vírus da hepatite B e C e de infecção oculta pelo vírus da hepatite B em pacientes com hanseníase na Paraíba
. (Doctoral Dissertation). Universidade Federal de Pernambuco. Retrieved from https://repositorio.ufpe.br/handle/123456789/24984
Chicago Manual of Style (16th Edition):
COSTA, Joanne Elizabeth Ferraz da. “Ocorrência de marcadores dos vírus da hepatite B e C e de infecção oculta pelo vírus da hepatite B em pacientes com hanseníase na Paraíba
.” 2017. Doctoral Dissertation, Universidade Federal de Pernambuco. Accessed March 04, 2021.
https://repositorio.ufpe.br/handle/123456789/24984.
MLA Handbook (7th Edition):
COSTA, Joanne Elizabeth Ferraz da. “Ocorrência de marcadores dos vírus da hepatite B e C e de infecção oculta pelo vírus da hepatite B em pacientes com hanseníase na Paraíba
.” 2017. Web. 04 Mar 2021.
Vancouver:
COSTA JEFd. Ocorrência de marcadores dos vírus da hepatite B e C e de infecção oculta pelo vírus da hepatite B em pacientes com hanseníase na Paraíba
. [Internet] [Doctoral dissertation]. Universidade Federal de Pernambuco; 2017. [cited 2021 Mar 04].
Available from: https://repositorio.ufpe.br/handle/123456789/24984.
Council of Science Editors:
COSTA JEFd. Ocorrência de marcadores dos vírus da hepatite B e C e de infecção oculta pelo vírus da hepatite B em pacientes com hanseníase na Paraíba
. [Doctoral Dissertation]. Universidade Federal de Pernambuco; 2017. Available from: https://repositorio.ufpe.br/handle/123456789/24984
University of New South Wales
8.
Alavi, Maryam.
Barriers to the assessment and treatment of Hepatitis C virus infection in people who inject drugs.
Degree: Kirby Institute, 2014, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/54298
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:34697/SOURCE02?view=true
► Background: Hepatitis C virus (HCV)-related morbidity and mortality are rising. Despite recent therapeutic advances, HCV assessment and treatment uptake remains suboptimal, particularly among people who…
(more)
▼ Background: Hepatitis C virus (
HCV)-related morbidity and mortality are rising. Despite recent therapeutic advances,
HCV assessment and treatment uptake remains suboptimal, particularly among people who inject drugs (PWID). Aims: The broad aim of this research was to inform barriers to the assessment and treatment of
HCV infection among PWID. Specific aims included evaluation of mortality and life expectancy among people with chronic
HCV infection; evaluation of
HCV treatment uptake and associated factors among inner city residents; evaluation of
HCV assessment and treatment uptake among PWID in opioid substitution setting; evaluation of willingness to receive
HCV treatment among PWID; and evaluation of the impact of treatment for
HCV infection on depression and mental health parameters.Methods: In Chapter Two, data from a population-based linkage study were analysed, using a competing risk methodology for calculation of mortality rates and life expectancy. In Chapter Three, data from the Community Health and Safety Evaluation (CHASE) cohort were analysed, using person-time and logistic regression methods. In Chapters Four and Five, data from the Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) study were analysed, using logistic regression. In Chapter Six, data from the Australian Trial in Acute Hepatitis C (ATAHC) study were analysed, using logistic regression. Key Findings: Among people with an
HCV notification, liver-related mortality is increasing. Life expectancy in this population is considerably lower, compared to the general population. Over the last decade,
HCV treatment uptake has slightly increased yet remained suboptimal. Integration of
HCV care within existing infrastructures for addiction care is successful in increasing
HCV assessment and treatment uptake among PWID. Despite low
HCV treatment uptake, treatment willingness is high among PWID and predicts subsequent assessment and treatment. PWID with poor social functioning may be most at risk of developing depression during
HCV therapy. However, depression prior to or during treatment does not have an impact on sustained virological response.Conclusion: Strategic public health planning is needed to lower the rising
HCV disease burden. Barriers to
HCV assessment and treatment among PWID are complex and require a multidimensional approach. Multidisciplinary partnerships are needed to expand access to
HCV services.
Advisors/Committee Members: Dore, Gregory, Faculty of Medicine, UNSW, Grebely, Jason, Faculty of Medicine, UNSW.
Subjects/Keywords: Treatment; PWID; HCV
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Alavi, M. (2014). Barriers to the assessment and treatment of Hepatitis C virus infection in people who inject drugs. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/54298 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:34697/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Alavi, Maryam. “Barriers to the assessment and treatment of Hepatitis C virus infection in people who inject drugs.” 2014. Doctoral Dissertation, University of New South Wales. Accessed March 04, 2021.
http://handle.unsw.edu.au/1959.4/54298 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:34697/SOURCE02?view=true.
MLA Handbook (7th Edition):
Alavi, Maryam. “Barriers to the assessment and treatment of Hepatitis C virus infection in people who inject drugs.” 2014. Web. 04 Mar 2021.
Vancouver:
Alavi M. Barriers to the assessment and treatment of Hepatitis C virus infection in people who inject drugs. [Internet] [Doctoral dissertation]. University of New South Wales; 2014. [cited 2021 Mar 04].
Available from: http://handle.unsw.edu.au/1959.4/54298 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:34697/SOURCE02?view=true.
Council of Science Editors:
Alavi M. Barriers to the assessment and treatment of Hepatitis C virus infection in people who inject drugs. [Doctoral Dissertation]. University of New South Wales; 2014. Available from: http://handle.unsw.edu.au/1959.4/54298 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:34697/SOURCE02?view=true
9.
Vounatsou, Myrsini.
Επιδημιολογία της λοίμωξης από τον ιό της ηπατίτιδας C σε ασθενείς κλινικής σεξουαλικών μεταδιδόμενων νοσημάτων και AIDS.
Degree: 2014, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
URL: http://hdl.handle.net/10442/hedi/41110
► In the present doctoral thesis we try to record epidemiology of Hepatitis C virus (HCV) in Greece, since there are no sufficient relative scientific studies…
(more)
▼ In the present doctoral thesis we try to record epidemiology of Hepatitis C virus (HCV) in Greece, since there are no sufficient relative scientific studies concerning our country.The collection of samples was performed in individuals who visited the Department of Sexually Transmitted Diseases and AIDS in “ANDREAS SYNGROS” Hospital during the period from 2004 till the end of 2012. 1.543 individuals were identified as positive to Hepatitis C (HCV) and these data consist the database of the present study.We applied Pearson statistical tool on this database and we attempted to statistically correlate with selective agents-variables, such as other STDs (Sexually Transmitted Diseases), age, sex, educational attainment, origin, sexual orientation, number of partners, usage of condom, usage of toxic substances, as well as with the parameter ‘economical refugee’.The laboratory methods used for the detection of HCV were the routine methods used in the Sexually Transmitted Diseases and AIDS Laboratory of ‘Andreas Syngros’ Hospital, which are immuno-serological and molecular methods. In the first case ELISA and immunoblotting methods were used, while the samples that gave uncertain result with the above mentioned methods were further proceeded with molecular detection.Studying the findings we noted that the most frequently observed groups by category are the following: in terms of toxic substances usage are the users of i.v. drugs, in terms of educational attainment are the elementary school graduates and higher education graduates, in terms of origin Greek people are far more prevalent, in terms of age the most popular group belongs to age category from 31 to 40 years old, in terms of gender men prevail, in terms of sexual orientation are the heterosexuals, in terms of number of partners are the ones with less than 5 partners during the last six months, in terms of coinfections presence the most common case is this of HIV, in terms of condom usage the highest percentage declares rare usage of condom and finally, in terms of the parameter ‘economical refugee’, only a small percentage belongs in this category.With respect to the joined variables HCV+STD, assessing a demographic characterization, our main conclusion was that only the parameter of age is representing a risk factor, while assessing an epidemiological characterization, our main conclusion was that the usage of toxic substances, the number of partners during the last six months and sexual orientation definitely are risk factors.The result of the present study is the accomplishment of an epidemiological study which can be used as a tool for clinicians, enabling them to categorize the potential carriers of the disease and contribute to early prognosis and timely treatment.
Στην παρούσα διδακτορική διατριβή γίνεται προσπάθεια καταγραφής της επιδημιολογίας του ιού της ηπατίτιδας C (HCV) στην Ελλάδα, καθώς δεν υπάρχουν αντίστοιχες επαρκείς επιστημονικές μελέτες στη χώρα μας.Η συλλογή των δειγμάτων αφορά σε άτομα που προσήλθαν στo Τμήμα Σεξουαλικώς Μεταδιδομένων…
Subjects/Keywords: Ηπατίτιδα C; Επιδημιολογία HCV; HCV-συλλοιμώξεις; ΣΜΝ; Hepatitis C; Eoidemiology HCV; HCV-HIV; HCV-coinfections; STDS
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Vounatsou, M. (2014). Επιδημιολογία της λοίμωξης από τον ιό της ηπατίτιδας C σε ασθενείς κλινικής σεξουαλικών μεταδιδόμενων νοσημάτων και AIDS. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/41110
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Vounatsou, Myrsini. “Επιδημιολογία της λοίμωξης από τον ιό της ηπατίτιδας C σε ασθενείς κλινικής σεξουαλικών μεταδιδόμενων νοσημάτων και AIDS.” 2014. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed March 04, 2021.
http://hdl.handle.net/10442/hedi/41110.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Vounatsou, Myrsini. “Επιδημιολογία της λοίμωξης από τον ιό της ηπατίτιδας C σε ασθενείς κλινικής σεξουαλικών μεταδιδόμενων νοσημάτων και AIDS.” 2014. Web. 04 Mar 2021.
Vancouver:
Vounatsou M. Επιδημιολογία της λοίμωξης από τον ιό της ηπατίτιδας C σε ασθενείς κλινικής σεξουαλικών μεταδιδόμενων νοσημάτων και AIDS. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2014. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10442/hedi/41110.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Vounatsou M. Επιδημιολογία της λοίμωξης από τον ιό της ηπατίτιδας C σε ασθενείς κλινικής σεξουαλικών μεταδιδόμενων νοσημάτων και AIDS. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2014. Available from: http://hdl.handle.net/10442/hedi/41110
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Indian Institute of Science
10.
Bhat, Prasanna.
Characterization of Host Protein Interactions with HCV RNA : Implications in Viral Translation, Replication and Design of Antivirals.
Degree: PhD, Faculty of Science, 2018, Indian Institute of Science
URL: http://etd.iisc.ac.in/handle/2005/3496
► HCV genome is a positive sense single-stranded RNA containing a single open reading frame (ORF) flanked by untranslated regions (UTRs), 5’UTR and 3’UTR.Initiation of HCV…
(more)
▼ HCV genome is a positive sense single-stranded RNA containing a single open reading frame (ORF) flanked by untranslated regions (UTRs), 5’UTR and 3’UTR.Initiation of
HCV RNA translation is mediated by internal ribosome entry site (IRES) present in 5’ UTR and this process is independent of cap-structure and requires only a small subset of canonical initiation factors. Hence,
HCV IRES-mediated translation initiation mechanism is quite different from canonical cellular mRNA translation initiation. The IRES is organized into highly structured domains, namely domain II, III and IV. High affinity interactions between structured RNA elements present in the IRES and 40S ribosomal proteins mediate 40S recruitment to
HCV IRES. However, details of the RNA elements and region of ribosomal proteins involved in these interactions are poorly understood. In recent days, RNA-based molecules like siRNAs, antisense RNAs and RNA decoys have become promising candidates for antiviral molecules. So designing short RNA molecules that target unique
HCV translation initiation mechanism might help in developing novel anti-
HCV molecules.
HCV 3’UTR and antisense-5’ UTRs serve as sites for replication initiation to synthesize negative and positive strand and this process is catalyzed by NS5B protein (RNA-dependent RNA polymerase). Hence, host proteins binding to both 3’UTR and antisense-5’UTR might play important role in
HCV replication. This puts the study of
HCV RNA–host protein interactions and its role in viral translation and replication in perspective.
Studying the
HCV IRES-ribosomal protein S5 interactions and its role in
HCV IRES function
Previous studies from our laboratory have demonstrated that binding of La protein to GCAC close to initiator AUG enhances ribosomal protein S5 (RPS5) binding with
HCV IRES and stimulates
HCV translation. However in-detail study on
HCV IRES–RPS5 interactions and its implication on
HCV translation initiation were lacking. In present study computational modelling suggested that domain II and IV interact majorly with the beta hairpin structure and C-terminal helix of RPS5. Filter-binding and UV cross-linking studies with peptides derived from predicated RNA-binding region of RPS5 and mutational studies with RPS5 demonstrated that beta hairpin structure present in RPS5 is critical for IRES–RPS5 interaction. In parallel, we have studied RNA elements involved in the IRES–RPS5 interactions using deletions and substitution mutations, which we had generated on the basis of the computational model. Direct and competition UV cross-linking experiments performed with these IRES mutants and 40S subunits as a source of RPS5 suggested that structure and sequence of both domain II and IV play crucial role in IRES–RPS5 interactions. We further investigated the effect of these mutations on IRES activity by in vitro translation assay and found that all the mutants that were compromised in binding to RPS5 showed reduced IRES activity. Moreover, ribosome assembly experiments on
HCV IRES demonstrated that mutations affecting…
Advisors/Committee Members: Das, Saumitra (advisor).
Subjects/Keywords: Hepatitis C Virus (HCV) RNA; HCV RNA Host Protein Interactions; HVC Infection; HCV RNA Translation; HCV Genomes; HCV Replication; HCV IRES RNA; HCV IRES; HCV Replication; HCV-IRES; HCV-IRES; HCV RNA; Virus-Host Protein Interactions; Viral RNA Replication; Microbiology and Cell Biology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bhat, P. (2018). Characterization of Host Protein Interactions with HCV RNA : Implications in Viral Translation, Replication and Design of Antivirals. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/3496
Chicago Manual of Style (16th Edition):
Bhat, Prasanna. “Characterization of Host Protein Interactions with HCV RNA : Implications in Viral Translation, Replication and Design of Antivirals.” 2018. Doctoral Dissertation, Indian Institute of Science. Accessed March 04, 2021.
http://etd.iisc.ac.in/handle/2005/3496.
MLA Handbook (7th Edition):
Bhat, Prasanna. “Characterization of Host Protein Interactions with HCV RNA : Implications in Viral Translation, Replication and Design of Antivirals.” 2018. Web. 04 Mar 2021.
Vancouver:
Bhat P. Characterization of Host Protein Interactions with HCV RNA : Implications in Viral Translation, Replication and Design of Antivirals. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2018. [cited 2021 Mar 04].
Available from: http://etd.iisc.ac.in/handle/2005/3496.
Council of Science Editors:
Bhat P. Characterization of Host Protein Interactions with HCV RNA : Implications in Viral Translation, Replication and Design of Antivirals. [Doctoral Dissertation]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/3496
11.
Da Costa, Daniel.
Study of cell host factors involved in Hepatitis C virus tropism : Etude des facteurs cellulaires de l'hôte impliqués dans le tropisme du virus de l'hépatite C.
Degree: Docteur es, Virologie : aspects moléculaires et médicaux, 2012, Université de Strasbourg
URL: http://www.theses.fr/2012STRAJ071
► Le virus de l’hépatite C (HCV) est un problème majeur de santé publique. Le développement de nouveaux traitements pour lutter contre le HCV a été…
(more)
▼ Le virus de l’hépatite C (HCV) est un problème majeur de santé publique. Le développement de nouveaux traitements pour lutter contre le HCV a été ralenti par l’absence de modèles d’études in vitro et in vivo convenables. Le but de mon travail de thèse a été, dans un premier temps, de caractériser les facteurs déterminant le tropisme hépatique du HCV. En exprimant des facteurs clés dans une lignée cellulaire humaine non-hépatocytaire, nous avons reconstitué in fine l’ensemble du cycle viral dans ces cellules. L’entrée du virus dans la cellule hôte fait intervenir différents récepteurs d’entrée dont CD81, occludin (OCLN), claudin-1 (CLDN1) et scavenger receptor class B type I (SR-BI). L’expression de ces quatre récepteurs sur cette lignée la rend hautement permissive à l’entrée du virus, mais ne permet pas de rétablir la réplication du virus. L’expression du micro-ARN 122, un micro-RNA important pour l’infection du HCV, dans les cellules exprimant les quatre récepteurs, restaure une forte réplication de l’ARN viral mais ne permet pas de détecter une production de particules infectieuses. L’expression de l’apolipoprotein E (apoE), jouant un rôle primordial dans l’assemblage et la sécrétion, rétablis cette dernière étape du cycle viral du HCV dans la lignée cellulaire humaine non-hépatocytaire. Dans un second temps, j’ai utilisé la stratégie, précédemment établie, pour étudier la spécificité d’espèce de l’infection du HCV dans plusieurs lignées hépatocytaires murines. Nous avons pu rendre ces cellules permissives à l’entrée du HCV et pu détecter une très faible réplication. L’ensemble de mes travaux apportent de nouvelles informations sur la compréhension des facteurs clés nécessaire au cycle viral du HCV dans des cellules murines et humaines.
Hepatitis C virus (HCV) is a global health burden. The development of new therapeutics to treat HCV infection has been hampered by the lack of convenient in vitro and in vivo model systems. The goal of my PhD work was, in a first time, to characterize the factors determining the hepatotropism of HCV. By expressing key factors within a non-hepatic cell line, we reconstituted in fine the full HCV life cycle in those cells. Virus entry into the host cell requires different entry factors which are CD81, occludin (OCLN), claudin-1 (CLDN1) and the scavenger receptor class B type I (SR-BI). The expression of these four factors in this cell line renders it highly permissive to viral entry, but does not allow restoring replication of the virus. The expression of miR-122, a micro-RNA important for HCV infection, into the cell lines expressing the four HCV entry factors restore a strong replication of the HCV RNA but does not allow detecting infectious viral particle production. Further expression of the apolipoprotein E (apoE), which plays a critical role in the assembly and release process, restore the last step of the HCV life cycle in a non-hepatic cell line. In a second part of my PhD, I have used the previously developed strategy to study the species specificity of HCV infection…
Advisors/Committee Members: Baumert, Thomas (thesis director).
Subjects/Keywords: Intéraction virus-hôte; Tropisme du HCV; Spécificité d’espèce du HCV; Entrée du HCV; Replication du HCV; Assemblage du HCV et modèle murin du HCV; Hepatitis C virus infection; Virus-host interaction; HCV tropism; HCV species specificity; HCV entry; HCV replication; HCV assembly and HCV mouse model; 579.2; 616.91; 572.8
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Da Costa, D. (2012). Study of cell host factors involved in Hepatitis C virus tropism : Etude des facteurs cellulaires de l'hôte impliqués dans le tropisme du virus de l'hépatite C. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2012STRAJ071
Chicago Manual of Style (16th Edition):
Da Costa, Daniel. “Study of cell host factors involved in Hepatitis C virus tropism : Etude des facteurs cellulaires de l'hôte impliqués dans le tropisme du virus de l'hépatite C.” 2012. Doctoral Dissertation, Université de Strasbourg. Accessed March 04, 2021.
http://www.theses.fr/2012STRAJ071.
MLA Handbook (7th Edition):
Da Costa, Daniel. “Study of cell host factors involved in Hepatitis C virus tropism : Etude des facteurs cellulaires de l'hôte impliqués dans le tropisme du virus de l'hépatite C.” 2012. Web. 04 Mar 2021.
Vancouver:
Da Costa D. Study of cell host factors involved in Hepatitis C virus tropism : Etude des facteurs cellulaires de l'hôte impliqués dans le tropisme du virus de l'hépatite C. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2012. [cited 2021 Mar 04].
Available from: http://www.theses.fr/2012STRAJ071.
Council of Science Editors:
Da Costa D. Study of cell host factors involved in Hepatitis C virus tropism : Etude des facteurs cellulaires de l'hôte impliqués dans le tropisme du virus de l'hépatite C. [Doctoral Dissertation]. Université de Strasbourg; 2012. Available from: http://www.theses.fr/2012STRAJ071
12.
西村, 知裕; ニシムラ, トモヒロ.
Clarification of the mechanism of p53 inactivation by the novel HCV infection-related protein 3β-hydroxysterol Δ24-reductase : シンキ HCV カンレン インシ 3β hydroxysterol Δ24 reductase ニ ヨル p53 キノウ ヨクセイ キコウ ノ カイメイ; 新規HCV関連因子 3β-hydroxysterol Δ24-reductase によるp53 機能抑制機構の解明.
Degree: Kumamoto University / 熊本大学
URL: http://hdl.handle.net/2298/21804
► The hepatitis C virus (HCV) is one of the most important causes of chronic liver disease. This chronic infection induces chronic hepatitis, hepatic cirrhosis and…
(more)
▼ The hepatitis C virus (HCV) is one of the most important causes of chronic liver disease. This chronic infection induces chronic hepatitis, hepatic cirrhosis and hematoma. The cause of the liver carcinoma is thought to be a long series of inflammation. But even now, the mechanism is not completely clarified. Thus I tried to analyzed host factor that was upregulated by the persistence expression of HCV genome, and elucidate of oncogenic mechanism of HCV infection. The purpose of this study was finding of new approach to the HCV therapy.
Subjects/Keywords: HCV; DHCR24
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
西村, 知裕; ニシムラ, . (n.d.). Clarification of the mechanism of p53 inactivation by the novel HCV infection-related protein 3β-hydroxysterol Δ24-reductase : シンキ HCV カンレン インシ 3β hydroxysterol Δ24 reductase ニ ヨル p53 キノウ ヨクセイ キコウ ノ カイメイ; 新規HCV関連因子 3β-hydroxysterol Δ24-reductase によるp53 機能抑制機構の解明. (Thesis). Kumamoto University / 熊本大学. Retrieved from http://hdl.handle.net/2298/21804
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
西村, 知裕; ニシムラ, トモヒロ. “Clarification of the mechanism of p53 inactivation by the novel HCV infection-related protein 3β-hydroxysterol Δ24-reductase : シンキ HCV カンレン インシ 3β hydroxysterol Δ24 reductase ニ ヨル p53 キノウ ヨクセイ キコウ ノ カイメイ; 新規HCV関連因子 3β-hydroxysterol Δ24-reductase によるp53 機能抑制機構の解明.” Thesis, Kumamoto University / 熊本大学. Accessed March 04, 2021.
http://hdl.handle.net/2298/21804.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
西村, 知裕; ニシムラ, トモヒロ. “Clarification of the mechanism of p53 inactivation by the novel HCV infection-related protein 3β-hydroxysterol Δ24-reductase : シンキ HCV カンレン インシ 3β hydroxysterol Δ24 reductase ニ ヨル p53 キノウ ヨクセイ キコウ ノ カイメイ; 新規HCV関連因子 3β-hydroxysterol Δ24-reductase によるp53 機能抑制機構の解明.” Web. 04 Mar 2021.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Vancouver:
西村, 知裕; ニシムラ . Clarification of the mechanism of p53 inactivation by the novel HCV infection-related protein 3β-hydroxysterol Δ24-reductase : シンキ HCV カンレン インシ 3β hydroxysterol Δ24 reductase ニ ヨル p53 キノウ ヨクセイ キコウ ノ カイメイ; 新規HCV関連因子 3β-hydroxysterol Δ24-reductase によるp53 機能抑制機構の解明. [Internet] [Thesis]. Kumamoto University / 熊本大学; [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2298/21804.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Council of Science Editors:
西村, 知裕; ニシムラ . Clarification of the mechanism of p53 inactivation by the novel HCV infection-related protein 3β-hydroxysterol Δ24-reductase : シンキ HCV カンレン インシ 3β hydroxysterol Δ24 reductase ニ ヨル p53 キノウ ヨクセイ キコウ ノ カイメイ; 新規HCV関連因子 3β-hydroxysterol Δ24-reductase によるp53 機能抑制機構の解明. [Thesis]. Kumamoto University / 熊本大学; Available from: http://hdl.handle.net/2298/21804
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
13.
ALBUQUERQUE, Diego Araújo Pessoa de.
Perfil Proteômico e Imunômico da Lectina Ligadora de Manose (Mbl) em Indivíduos Portadores do Vírus da Hepatite
.
Degree: 2010, Universidade Federal de Pernambuco
URL: http://repositorio.ufpe.br/handle/123456789/1811
► A lectina ligadora de manose (mannan binding lectin - MBL) é membro das glicoproteínas plasmáticas, um grupo de proteínas que se caracteriza pela interação com…
(more)
▼ A lectina ligadora de manose (mannan binding lectin - MBL) é membro das glicoproteínas
plasmáticas, um grupo de proteínas que se caracteriza pela interação com um ou mais resíduos
de açúcares específicos expressos em vários sistemas biológicos. Concentrações reduzidas de
MBL tem sido relacionadas com a diminuição na resposta a varias doenças infecciosas.
Inúmeras formas oligoméricas da MBL, com diferentes capacidades funcionais, são
encontradas no sangue humano. Estudos controversos lidam com a possível associação entre
mutações no gene da MBL e a infecção com o vírus da hepatite C (hepatitis C vírus -
HCV).
Não existem associações significativas entre pacientes com baixos níveis séricos de MBL e as
características de desenvolvimento da doença, incluindo a resposta a terapia antiviral. O
presente estudo teve como objetivo propor um ensaio prático para purificação de formas
moleculares de MBL em amostras de soro de pacientes infectados com
HCV visando
investigar a estrutura e o genótipo desta lectina. Os resultados do ensaio de dot-N-man
demonstraram uma boa eficiência na separação da MBL utilizando membrana de
nitrocelulose revestida de manana. A identificação de MBL foi confirmada em todos os
genótipos por método convencional de dot-ELISA. Bandas protéicas em gel de eletroforese
revelaram diferentes padrões de migração entre os genótipos AA, A0 e 00, entre 50-90 KDa, e
270 KDa, relacionadas com a variação de baixa e alta massa molecular da subunidade
estrutural de MBL, respectivamente. Nas amostras de SDS-PAGE não redutora observou-se
uma maior variedade de massas moleculares, como dímeros, trímeros, e as unidades
estruturais de MBL, principalmente em indivíduos AA. A analise de western blotting
confirmou a presença de alta (128 KDa) e baixa (32KDa) massas moleculares da MBL. Foi
também observada a presença de MBL com massa molecular de 128 KDa, a qual não é muito
comum. Os resultados mostraram que ambas, baixa e alta formas moleculares, foram
identificadas e também houve variação com a genotipagem dos pacientes. Os resultados
descrevendo o proteoma das formas moleculares de MBL em pacientes com
HCV
contribuíram para melhor compreensão da estrutura/genótipo da MBL nesta patologia que
pode estar associada à resposta ao tratamento
Advisors/Committee Members: CARVALHO JUNIOR, Luiz Bezerra de (advisor).
Subjects/Keywords: dot-N-man;
HCV;
MBL
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
ALBUQUERQUE, D. A. P. d. (2010). Perfil Proteômico e Imunômico da Lectina Ligadora de Manose (Mbl) em Indivíduos Portadores do Vírus da Hepatite
. (Thesis). Universidade Federal de Pernambuco. Retrieved from http://repositorio.ufpe.br/handle/123456789/1811
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
ALBUQUERQUE, Diego Araújo Pessoa de. “Perfil Proteômico e Imunômico da Lectina Ligadora de Manose (Mbl) em Indivíduos Portadores do Vírus da Hepatite
.” 2010. Thesis, Universidade Federal de Pernambuco. Accessed March 04, 2021.
http://repositorio.ufpe.br/handle/123456789/1811.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
ALBUQUERQUE, Diego Araújo Pessoa de. “Perfil Proteômico e Imunômico da Lectina Ligadora de Manose (Mbl) em Indivíduos Portadores do Vírus da Hepatite
.” 2010. Web. 04 Mar 2021.
Vancouver:
ALBUQUERQUE DAPd. Perfil Proteômico e Imunômico da Lectina Ligadora de Manose (Mbl) em Indivíduos Portadores do Vírus da Hepatite
. [Internet] [Thesis]. Universidade Federal de Pernambuco; 2010. [cited 2021 Mar 04].
Available from: http://repositorio.ufpe.br/handle/123456789/1811.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
ALBUQUERQUE DAPd. Perfil Proteômico e Imunômico da Lectina Ligadora de Manose (Mbl) em Indivíduos Portadores do Vírus da Hepatite
. [Thesis]. Universidade Federal de Pernambuco; 2010. Available from: http://repositorio.ufpe.br/handle/123456789/1811
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Alberta
14.
Samrat, Subodh Kr.
MODULATION OF IMMUNE RESPONSE BY HCV-DERIVED F, CORE AND NS3
PROTEINS.
Degree: PhD, Department of Surgery, 2013, University of Alberta
URL: https://era.library.ualberta.ca/files/vm40xt06s
► The hepatitis C virus leads to chronic infection in the majority of infected individuals; however, in a minority of patients, acute infection is followed by…
(more)
▼ The hepatitis C virus leads to chronic infection in
the majority of infected individuals; however, in a minority of
patients, acute infection is followed by viral clearance. The
immune correlates of viral clearance are not yet clear, but have
been extensively investigated, suggesting the role of multispecific
and multifunctional cellular immunity. In the current studies, we
demonstrated that endogenous expression of the F protein in human
DCs leads to contrasting effects on activation and apoptosis of
DCs, allowing the activated DCs to efficiently internalize
apoptotic DCs. These in turn result in the efficient ability of DCs
to process and present antigen, and prime and stimulate
antigen-specific T cells from HCV-naive individuals. Our in vivo
studies show that mice immunized with F- or core-containing
adenovector induce dysfunctional T cells with reduced granzyme B
(GrB) expression which are unable to kill peptide-loaded target
cells. Exogenous addition of IL-2 in in vitro cultures, as well as
immunization with the toll-like receptor (TLR) agonist poly I:C
restores the GrB expression in T cells. Thus, we have discovered a
new mechanism of T cell modulation by HCV-derived antigens and we
have also delineated strategies to overcome this dysfunction.
Further, we have analyzed the early immune events in the mice
immunized with recombinant adenovector containing core and NS3 in a
time-course manner. Our results demonstrate that despite efficient
expression of both antigens at the site of immunization, T cell
proliferation and IL-2, IL-6 and IL-12 production were
significantly higher in NS3-immunized mice at 12-48 hours after
immunization compared to the core-immunized mice. These studies
have implied that early events in antigen encounters imprint the
subsequent immunity and the final outcome; two distinct patterns of
early events in immunity can be demonstrated for the antigens core
and NS3. Over all, my studies have discovered a new mechanism of
immune modulation by HCV-derived antigens that could help in
designing both prophylactic and therapeutic vaccine candidates
against the HCV.
Subjects/Keywords: HCV; Immunology; DCs modulation
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Samrat, S. K. (2013). MODULATION OF IMMUNE RESPONSE BY HCV-DERIVED F, CORE AND NS3
PROTEINS. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/vm40xt06s
Chicago Manual of Style (16th Edition):
Samrat, Subodh Kr. “MODULATION OF IMMUNE RESPONSE BY HCV-DERIVED F, CORE AND NS3
PROTEINS.” 2013. Doctoral Dissertation, University of Alberta. Accessed March 04, 2021.
https://era.library.ualberta.ca/files/vm40xt06s.
MLA Handbook (7th Edition):
Samrat, Subodh Kr. “MODULATION OF IMMUNE RESPONSE BY HCV-DERIVED F, CORE AND NS3
PROTEINS.” 2013. Web. 04 Mar 2021.
Vancouver:
Samrat SK. MODULATION OF IMMUNE RESPONSE BY HCV-DERIVED F, CORE AND NS3
PROTEINS. [Internet] [Doctoral dissertation]. University of Alberta; 2013. [cited 2021 Mar 04].
Available from: https://era.library.ualberta.ca/files/vm40xt06s.
Council of Science Editors:
Samrat SK. MODULATION OF IMMUNE RESPONSE BY HCV-DERIVED F, CORE AND NS3
PROTEINS. [Doctoral Dissertation]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/vm40xt06s
15.
Papachristou, Eleni.
Μελέτη της πολυμορφίας του HCV στην Ελλάδα: αναζήτηση σπανίων στελεχών και μέθοδοι προσδιορισμού τους.
Degree: 2017, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
URL: http://hdl.handle.net/10442/hedi/41393
► The discovery of the HCV virus as the etiologic factor for the non A, non B hepatitis cases, led to the development of many methods…
(more)
▼ The discovery of the HCV virus as the etiologic factor for the non A, non B hepatitis cases, led to the development of many methods and technologies for its detection and identification. HCV is a flavivirus and its genome is a single stranded RNA molecule which encodes for a polyprotein which provides the structural and non structural proteins of the virus. The target cells for HCV are the hepatocytes as well as B and T lymphocytes, dendritic and mononuclear cells which the virus enters throygh endocytosis. Although the immune system manages to clear the virus a large number (80-85%) of patients become chronic carriers from which about 5-25% will develop chirrossis, end stage liver disease and hepatocellular carcinoma.HCV has a great genetic diversity, is spread worldwide having infected more than 150 million of people and is classified in seven major genotypes and many subtypes. The detection and quantification of thw HCV RNA are valuable tools for monitoring the chronic infection and the outcome of the therapy. Furthermore, knowing the genotype with which a patient is infected is crucial for the choice of the therary regimen. The aim of this study was to develop two in house methods a) for the detection and quantification of the HCV RNA and b) for the determination of the genotype in order to study the diversity of HCV in Greece.For the quantification method we targeted at the 3’UTR end of the genome in contrast to all the commercially available methods which target the 5’end. After experimenting with different types of reagents and enzymes and on different platforms we finally chose the technology of one step real time RT PCR on the Light Cycler platform (Roche). The method was validated with international standards and was evaluated with two commercially available methods from Abbott and Roche with excellent results. The method is quick, reliable and low cost and can be further developed.For the HCV genotyping we developed a method based on the sequencing of the NS5B region of the genome. We designed primers and tried many PCR protocols. The obtained sequences were analysed with phylogenetic analysis methods. The method was validated with international standards and was certified by ΕΣΥΔ. With this method we genotyped most of the undetermined samples (by other methods) in our lab and mainly we studied the HCV dispersal pattern among IDUs (intravenous drug users) in Athens as part of the “Aristotle” programme.
Η ανακάλυψη και ταυτοποίηση του ιού HCV ως τον αιτιολογικό παράγοντα των περιστατικών μη-Α, μη-Β ηπατίτιδας ήταν η αρχή για την ανάπτυξη διαφόρων μεθόδων και τεχνολογιών για την ανίχνευση και τυποποίησή του. Ο ιός HCV ανήκει στην οικογένεια Flaviviridae, γένος hepacivirus και το γονιδίωμά του είναι μονόκλωνο RNA θετικής πολικότητας που κωδικοποιεί μια πολυπρωτεϊνη από την οποία προκύπτουν οι δομικές και οι μη δομικές πρωτεϊνες του. Κύτταρα-στόχοι του ιού – στα οποία εισέρχεται με ενδοκύτωση μετά από πρόσδεση σε ειδικούς υποδοχείς- είναι τα ηπατοκύτταρα αλλά αναφέρονται και τα λεμφοκύτταρα (Β και Τ) καθώς…
Subjects/Keywords: Ηπατίτιδα C; HCV-RNA; Γονότυπος HCV; ΧΕΝ; Δίκτυα μετάδοσης; Hepatitis C; HCV-RNA; HCV genotype; IDU; Transmission networks
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Papachristou, E. (2017). Μελέτη της πολυμορφίας του HCV στην Ελλάδα: αναζήτηση σπανίων στελεχών και μέθοδοι προσδιορισμού τους. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/41393
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Papachristou, Eleni. “Μελέτη της πολυμορφίας του HCV στην Ελλάδα: αναζήτηση σπανίων στελεχών και μέθοδοι προσδιορισμού τους.” 2017. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed March 04, 2021.
http://hdl.handle.net/10442/hedi/41393.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Papachristou, Eleni. “Μελέτη της πολυμορφίας του HCV στην Ελλάδα: αναζήτηση σπανίων στελεχών και μέθοδοι προσδιορισμού τους.” 2017. Web. 04 Mar 2021.
Vancouver:
Papachristou E. Μελέτη της πολυμορφίας του HCV στην Ελλάδα: αναζήτηση σπανίων στελεχών και μέθοδοι προσδιορισμού τους. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2017. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10442/hedi/41393.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Papachristou E. Μελέτη της πολυμορφίας του HCV στην Ελλάδα: αναζήτηση σπανίων στελεχών και μέθοδοι προσδιορισμού τους. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2017. Available from: http://hdl.handle.net/10442/hedi/41393
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Texas A&M University
16.
Reddy Chinnaswamy, Sreedhar.
De Novo Initiated RNA Synthesis by the Hepatitis C Virus RNA-dependent RNA Polymerase.
Degree: PhD, Biochemistry, 2011, Texas A&M University
URL: http://hdl.handle.net/1969.1/ETD-TAMU-2010-05-7816
► Hepatitis C Virus (HCV) is a positive-strand RNA virus that has infected more than 3% of the world population. Chronic infections by the virus lead…
(more)
▼ Hepatitis C Virus (
HCV) is a positive-strand RNA virus that has infected more than 3% of the world population. Chronic infections by the virus lead to cirrhosis and hepatocellular carcinoma.
HCV is currently the leading cause for liver transplantation in the US. The nonstructural protein NS5B of
HCV is the RNA-dependent RNA polymerase (RdRp) that replicates the viral RNA on host derived membranous structures.
Structurally NS5B has the characteristic fingers, thumb and palm domains seen in all polymerase proteins. However, extensive interactions between the fingers and thumb domains completely encircle the active site of NS5B as seen in solved X-ray diffraction crystal structures. These interactions are primarily mediated by a short (35 residues) flexible loop called the Delta 1 loop. NS5B produced from heterologous systems can initiate RNA synthesis by a de novo initiation mechanism from 3?ends of RNA templates or can also extend from 3'ends of primers that are annealed stably to a template RNA in biochemical assays. The closed conformation of NS5B as per X-ray crystal structures can only accommodate a ssRNA but not a dsRNA, hence necessitating a conformational change between de novo initiation and elongation. The details of these conformational changes are not known and will prove to be important to design potent polymerase inhibitors. The study performed for this dissertation focused on the conformational requirements of NS5B during de novo initiation and primer extension (or elongation). Biochemical assays utilizing template RNAs that can lead to both de novo initiation and primer extension products were utilized, and a systematic mutational analysis of the template channel of the RdRp was performed. Mutants W397A and H428A were identified that showed only primer extension but no de novo initiation. Structural analysis of NS5B suggested that these residues were important contact points in the Delta 1 loop and thumb domain interactions. A deletion mutant, m26-30 with a five amino acid deletion at the apex of the Delta 1 loop also failed in de novo initiation but not primer extension reactions. Biophysical and gel shift assays showed that m26-30 was in a more open conformation than the WT enzyme. Furthermore, oligomerization of NS5B was demonstrated and its role in RNA synthesis was examined. It was found that the de novo initiation competent conformation of NS5B is maintained by oligomeric contacts between individual subunits, likely by stabilizing the Delta 1 loop and thumb domain interactions. Mutations disrupting the Delta 1 loop and thumb domain interactions as well as those in the allosteric GTP binding site induced conformational changes in the protein partially explaining the defect in de novo initiation activity in enzymes carrying those mutations. These results not only contribute to the overall mechanism of RNA synthesis in viral RdRps but also open new avenues for developing
HCV polymerase inhibitors.
Advisors/Committee Members: Kao, Cheng C. (advisor), Young, Ryland F. (advisor), Leibowitz, Julian L. (committee member), Scholtz, Martin J. (committee member).
Subjects/Keywords: HCV; RdRp; Polymerase; Conformation; Oligomerization
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Reddy Chinnaswamy, S. (2011). De Novo Initiated RNA Synthesis by the Hepatitis C Virus RNA-dependent RNA Polymerase. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2010-05-7816
Chicago Manual of Style (16th Edition):
Reddy Chinnaswamy, Sreedhar. “De Novo Initiated RNA Synthesis by the Hepatitis C Virus RNA-dependent RNA Polymerase.” 2011. Doctoral Dissertation, Texas A&M University. Accessed March 04, 2021.
http://hdl.handle.net/1969.1/ETD-TAMU-2010-05-7816.
MLA Handbook (7th Edition):
Reddy Chinnaswamy, Sreedhar. “De Novo Initiated RNA Synthesis by the Hepatitis C Virus RNA-dependent RNA Polymerase.” 2011. Web. 04 Mar 2021.
Vancouver:
Reddy Chinnaswamy S. De Novo Initiated RNA Synthesis by the Hepatitis C Virus RNA-dependent RNA Polymerase. [Internet] [Doctoral dissertation]. Texas A&M University; 2011. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2010-05-7816.
Council of Science Editors:
Reddy Chinnaswamy S. De Novo Initiated RNA Synthesis by the Hepatitis C Virus RNA-dependent RNA Polymerase. [Doctoral Dissertation]. Texas A&M University; 2011. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2010-05-7816
Texas A&M University
17.
Simeon, Rudo Lyndon.
Selecting a path against Hepatitis C Virus.
Degree: PhD, Chemical Engineering, 2013, Texas A&M University
URL: http://hdl.handle.net/1969.1/151941
► Hepatitis C virus (HCV) currently affects ~5% of the world’s population and has relatively limited treatment options for infected patients. Genetic suppressor elements (GSE) derived…
(more)
▼ Hepatitis C virus (
HCV) currently affects ~5% of the world’s population and has relatively limited treatment options for infected patients. Genetic suppressor elements (GSE) derived from a gene or genome of interest can act as transdominant inhibitors of a particular biology function presumably by binding to and blocking an essential interaction surface for protein activity. Taking advantage of hepatoma cell line n4mBid, that supports all stages of the
HCV life cycle and strongly report
HCV infection by a cell-death phenotype, we developed an iterative selection/enrichment strategy for the identification of GSE against
HCV. Using this strategy, a library expressing random fragments of the
HCV genome was screened for sequences able to suppress
HCV infection. A 244 amino acid gene fragment, B1, was strongly enriched after 5 rounds of selection. B1 has a very high net positive charge of 43 at neutral pH and a high charge-to-mass (kDa) ratio of 1.5. We show that B1 expression specifically inhibits
HCV replication, apparently due to its high positive charge. We also show that recombinant positively charged proteins can inhibit
HCV infection, when supplied in vitro.In addition, eGFP-fused B1 potently penetrates both adherent and suspension cells with >80% of cells taking up the protein. Importantly, we show that B1 not only facilitates cellular uptake, but allows protein cargo to reach sites of biological relevance. B1 also delivers non-covalently conjugated RNA and DNA across the cell membrane to cytosolic and nuclear sites, with efficiency comparable to commercially available cationic lipid reagents. Our data suggest that B1 utilizes cell-surface glycans and multiple competing endocytic pathways to enter and traffic through cells.During a separate screening carried out in our lab, we identified a TACR3 inhibitor SB 222200 that had significant
HCV activity. We go on to show that both TACR1 and TACR3 receptors are expressed in the
HCV-permissive Huh 7.5 cell line. We also show that both TACR1 and TACR3 inhibitors significantly inhibit
HCV infection. These results point to the potential for TACR1 antagonists in treating patients infected with both
HCV and HIV.
Advisors/Committee Members: Chen, Zhilei (advisor), Jayaraman, Arul (committee member), Karim, Nazmul (committee member), Leibowitz, Julian (committee member).
Subjects/Keywords: HCV; biomolecules; biotherapeutics; transfection; transduction
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Simeon, R. L. (2013). Selecting a path against Hepatitis C Virus. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/151941
Chicago Manual of Style (16th Edition):
Simeon, Rudo Lyndon. “Selecting a path against Hepatitis C Virus.” 2013. Doctoral Dissertation, Texas A&M University. Accessed March 04, 2021.
http://hdl.handle.net/1969.1/151941.
MLA Handbook (7th Edition):
Simeon, Rudo Lyndon. “Selecting a path against Hepatitis C Virus.” 2013. Web. 04 Mar 2021.
Vancouver:
Simeon RL. Selecting a path against Hepatitis C Virus. [Internet] [Doctoral dissertation]. Texas A&M University; 2013. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1969.1/151941.
Council of Science Editors:
Simeon RL. Selecting a path against Hepatitis C Virus. [Doctoral Dissertation]. Texas A&M University; 2013. Available from: http://hdl.handle.net/1969.1/151941
Texas A&M University
18.
Chamoun Emanuelli, Ana M.
Characterization of Viral Entry Inhibitors.
Degree: PhD, Chemical Engineering, 2014, Texas A&M University
URL: http://hdl.handle.net/1969.1/153447
► Hepatitis C virus (HCV), Human Immunodeficiency virus (HIV) and Herpes Simplex virus (HSV) are pathogenic viruses known to cause liver disorder, acquired immunodeficiency and skin…
(more)
▼ Hepatitis C virus (
HCV), Human Immunodeficiency virus (HIV) and Herpes Simplex virus (HSV) are pathogenic viruses known to cause liver disorder, acquired immunodeficiency and skin lesions, respectively. Although current therapies have played substantial roles in the fight against these pathogens, their use is limited and for the most part does not result in viral eradication. Moreover, most antivirals target viral encoded structures which overtime foster the development of resistant strains. Hence, antivirals aimed at preventing initial infection represent a promising strategy for viral combat.
This dissertation focuses on the characterization of viral entry inhibitors and their potential use. The first compounds evaluated come from the phenothiazines family, widely used as antipsychotic drugs. Phenothiazines were shown to suppress
HCV entry by intercalating into cholesterol-rich membrane domains of target cells thus reducing viral-host fusion.
The second candidates studied are two members of the H1-anthistamines currently used for allergy treatment. Both compounds strongly reduce
HCV entry, likely at the fusion step, and its inhibition was associated with cholesterol content in the virion and host cells, pointing to the use of an NPC1L1-receptor dependent mechanism.
Lastly, we evaluated the antiviral activity of PD 404,182 (PD) as an alternate treatment for
HCV-HIV coinfected patients as well as its potential use as an anti-HIV microbicide. PD is able to reduce viral entry of the three pathogens through physical disruption of virions releasing the nucleic acids into the surrounding medium. Moreover, PD possesses several qualities pointing to its use as a potential microbicide.
Advisors/Committee Members: Chen, Zhilei (advisor), Jayaraman, Arul (committee member), Kao, Katy (committee member), Welsh, Jane (committee member).
Subjects/Keywords: HCV; HSV; HIV; entry inhibitors
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chamoun Emanuelli, A. M. (2014). Characterization of Viral Entry Inhibitors. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/153447
Chicago Manual of Style (16th Edition):
Chamoun Emanuelli, Ana M. “Characterization of Viral Entry Inhibitors.” 2014. Doctoral Dissertation, Texas A&M University. Accessed March 04, 2021.
http://hdl.handle.net/1969.1/153447.
MLA Handbook (7th Edition):
Chamoun Emanuelli, Ana M. “Characterization of Viral Entry Inhibitors.” 2014. Web. 04 Mar 2021.
Vancouver:
Chamoun Emanuelli AM. Characterization of Viral Entry Inhibitors. [Internet] [Doctoral dissertation]. Texas A&M University; 2014. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1969.1/153447.
Council of Science Editors:
Chamoun Emanuelli AM. Characterization of Viral Entry Inhibitors. [Doctoral Dissertation]. Texas A&M University; 2014. Available from: http://hdl.handle.net/1969.1/153447
University of Toronto
19.
Khattar, Ramzi.
Targeted Deletion of Fibrinogen-like Protein 2 (FGL2) ENHANCES Immunity in a Murine Model of Acute Viral Hepatitis Caused by Lymphocytic Choriomeningitis Virus (LCMV).
Degree: 2011, University of Toronto
URL: http://hdl.handle.net/1807/31278
► Viral hepatitis infection represents a significant epidemiological and economic burden on society. Following infection, some patients mount a blunted immune response to the virus, which…
(more)
▼ Viral hepatitis infection represents a significant epidemiological and economic burden on society. Following infection, some patients mount a blunted immune response to the virus, which ultimately can result in chronic infection. FGL2, a member of the fibrinogen-related protein superfamily, has been implicated in vitro in suppressing both innate and adaptive immune responses. In a murine model of acute viral hepatitis caused by Lymphocytic Choriomeningitis Virus strain WE, we demonstrate that FGL2 expressed by reticuloendothelial cells limits viral spread. When expressed by Treg cells FGL2 binds to FCγRIIB and prevents DC maturation and suppresses virus-specific T and B cell responses. We provide compelling evidence to suggest that hepatitis viruses utilize the FGL2-FCγRIIB pathway to evade immune detection. Inhibition of this pathway restores effective cellular and humoral antiviral immune responses towards hepatitis viruses.
MAST
Advisors/Committee Members: Levy, Gary A., Immunology.
Subjects/Keywords: LCMV; HCV pathogenesis; 0982
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Khattar, R. (2011). Targeted Deletion of Fibrinogen-like Protein 2 (FGL2) ENHANCES Immunity in a Murine Model of Acute Viral Hepatitis Caused by Lymphocytic Choriomeningitis Virus (LCMV). (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/31278
Chicago Manual of Style (16th Edition):
Khattar, Ramzi. “Targeted Deletion of Fibrinogen-like Protein 2 (FGL2) ENHANCES Immunity in a Murine Model of Acute Viral Hepatitis Caused by Lymphocytic Choriomeningitis Virus (LCMV).” 2011. Masters Thesis, University of Toronto. Accessed March 04, 2021.
http://hdl.handle.net/1807/31278.
MLA Handbook (7th Edition):
Khattar, Ramzi. “Targeted Deletion of Fibrinogen-like Protein 2 (FGL2) ENHANCES Immunity in a Murine Model of Acute Viral Hepatitis Caused by Lymphocytic Choriomeningitis Virus (LCMV).” 2011. Web. 04 Mar 2021.
Vancouver:
Khattar R. Targeted Deletion of Fibrinogen-like Protein 2 (FGL2) ENHANCES Immunity in a Murine Model of Acute Viral Hepatitis Caused by Lymphocytic Choriomeningitis Virus (LCMV). [Internet] [Masters thesis]. University of Toronto; 2011. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1807/31278.
Council of Science Editors:
Khattar R. Targeted Deletion of Fibrinogen-like Protein 2 (FGL2) ENHANCES Immunity in a Murine Model of Acute Viral Hepatitis Caused by Lymphocytic Choriomeningitis Virus (LCMV). [Masters Thesis]. University of Toronto; 2011. Available from: http://hdl.handle.net/1807/31278
20.
GOMES, Daniel Christiano de Albuquerque.
Disfunção cognitiva em pacientes com infecção crônica pelo vírus da hepatite C: estudo transversal na cidade do Recife e revisão de literatura
.
Degree: 2011, Universidade Federal de Pernambuco
URL: https://repositorio.ufpe.br/handle/123456789/29281
► A hepatite C crônica constitui atualmente importante problema de saúde pública, visto que acomete cerca de 2% da população mundial. Representa uma das principais causas…
(more)
▼ A hepatite C crônica constitui atualmente importante problema de saúde pública, visto que acomete cerca de 2% da população mundial. Representa uma das principais causas de cirrose hepática, hepatocarcinoma e transplante hepático. Embora suas principais conseqüências se devam ao comprometimento hepático, manifestações extra-hepáticas da doença têm sido bem documentadas. Ao longo dos últimos anos, pesquisas com a utilização de diferentes ferramentas diagnósticas têm apontado a ocorrência de disfunção cognitiva nesta população. O presente trabalho é composto por dois artigos. O primeiro deles é um artigo de revisão, o qual visa a abordar as evidências mais atuais dos efeitos neurocognitivos da infecção crônica pelo
HCV. São revisados os tipos e a prevalência de alterações cerebrais identificadas nos variados métodos diagnósticos empregados, assim como os mecanismos patogênicos propostos para a disfunção cognitiva. Embora sejam notadas controvérsias na literatura revisada, identifica-se que prejuízos em atenção, velocidade de processamento mental e memória de trabalho têm sido os mais comumente descritos na hepatite C crônica, configurando um padrão compatível com disfunção frontal-subcortical. Além disso, na parte final do artigo, são comentados os principais impactos da co-infecção
HCV/HIV e da terapia antiviral à cognição.Já o segundo é um artigo original, que descreve um estudo transversal realizado em Recife, no Nordeste do Brasil. A pesquisa objetivou avaliar, através da aplicação de testes neuropsicológicos, a ocorrência de déficits cognitivos numa amostra constituída por pacientes não cirróticos com hepatite C crônica, inclusos no grupo de casos, e indivíduos curados da infecção pelo
HCV, estes pertencentes ao grupo controle. Foram excluídos do estudo indivíduos com condições clínicas que sabidamente acarretam declínio cognitivo. Identificou-se elevada ocorrência de desempenho deficitário em ambos os grupos em vários dos testes aplicados, sobretudo em medidas de atenção, velocidade de processamento mental, flexibilidade mental e memória de trabalho. Diferentemente do que tem sido descrito na literatura, o presente estudo evidenciou ainda ocorrência significativa de déficits em habilidades aritméticas e construcionais visuoespaciais. Entre os grupos, houve diferenças significativas apenas em dois subtestes de linguagem, com pior desempenho do grupo de casos. Este trabalho, portanto, corroborou alguns dos achados previamente referidos na literatura, bem como evidenciou peculiaridades até então pouco descritas.
Advisors/Committee Members: LOPES NETO, Edmundo Pessoa de Almeida (advisor), http://lattes.cnpq.br/1738354802121443 (advisor).
Subjects/Keywords: Hepatite C;
HCV;
Disfunção cognitiva
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
GOMES, D. C. d. A. (2011). Disfunção cognitiva em pacientes com infecção crônica pelo vírus da hepatite C: estudo transversal na cidade do Recife e revisão de literatura
. (Masters Thesis). Universidade Federal de Pernambuco. Retrieved from https://repositorio.ufpe.br/handle/123456789/29281
Chicago Manual of Style (16th Edition):
GOMES, Daniel Christiano de Albuquerque. “Disfunção cognitiva em pacientes com infecção crônica pelo vírus da hepatite C: estudo transversal na cidade do Recife e revisão de literatura
.” 2011. Masters Thesis, Universidade Federal de Pernambuco. Accessed March 04, 2021.
https://repositorio.ufpe.br/handle/123456789/29281.
MLA Handbook (7th Edition):
GOMES, Daniel Christiano de Albuquerque. “Disfunção cognitiva em pacientes com infecção crônica pelo vírus da hepatite C: estudo transversal na cidade do Recife e revisão de literatura
.” 2011. Web. 04 Mar 2021.
Vancouver:
GOMES DCdA. Disfunção cognitiva em pacientes com infecção crônica pelo vírus da hepatite C: estudo transversal na cidade do Recife e revisão de literatura
. [Internet] [Masters thesis]. Universidade Federal de Pernambuco; 2011. [cited 2021 Mar 04].
Available from: https://repositorio.ufpe.br/handle/123456789/29281.
Council of Science Editors:
GOMES DCdA. Disfunção cognitiva em pacientes com infecção crônica pelo vírus da hepatite C: estudo transversal na cidade do Recife e revisão de literatura
. [Masters Thesis]. Universidade Federal de Pernambuco; 2011. Available from: https://repositorio.ufpe.br/handle/123456789/29281
Kwame Nkrumah University of Science and Technology
21.
Layden, Jennifer E.; Phillips, Richard O.; Owusu-Ofori, Shirley; Sarfo, Fred Stephen; Kliethermes, Stephanie.
High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways.
Degree: 2014, Kwame Nkrumah University of Science and Technology
URL: http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11855
► Sub-Saharan Africa (SSA) has one of the highest global hepatitis C virus (HCV) prevalence estimates. However, reports that suggest high rates of serologic false positives…
(more)
▼ Sub-Saharan Africa (SSA) has one of the highest global hepatitis C virus (HCV) prevalence estimates.
However, reports that suggest high rates of serologic false positives and low levels of viremia have led to uncertainty
regarding the burden of active infection in this region. Additionally, little is known about the predominant
transmission risk factors in SSA.
An article published by Oxford University Press and available at DOI: 10.1093/cid/ciu965
KNUST
Subjects/Keywords: HCV; Africa; prevalence; transmission.
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Layden, Jennifer E.; Phillips, Richard O.; Owusu-Ofori, Shirley; Sarfo, Fred Stephen; Kliethermes, S. (2014). High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways. (Thesis). Kwame Nkrumah University of Science and Technology. Retrieved from http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11855
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Layden, Jennifer E.; Phillips, Richard O.; Owusu-Ofori, Shirley; Sarfo, Fred Stephen; Kliethermes, Stephanie. “High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways.” 2014. Thesis, Kwame Nkrumah University of Science and Technology. Accessed March 04, 2021.
http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11855.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Layden, Jennifer E.; Phillips, Richard O.; Owusu-Ofori, Shirley; Sarfo, Fred Stephen; Kliethermes, Stephanie. “High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways.” 2014. Web. 04 Mar 2021.
Vancouver:
Layden, Jennifer E.; Phillips, Richard O.; Owusu-Ofori, Shirley; Sarfo, Fred Stephen; Kliethermes S. High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways. [Internet] [Thesis]. Kwame Nkrumah University of Science and Technology; 2014. [cited 2021 Mar 04].
Available from: http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11855.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Layden, Jennifer E.; Phillips, Richard O.; Owusu-Ofori, Shirley; Sarfo, Fred Stephen; Kliethermes S. High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways. [Thesis]. Kwame Nkrumah University of Science and Technology; 2014. Available from: http://dspace.knust.edu.gh:8080/jspui/handle/123456789/11855
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Harvard University
22.
Stoeckle, Catherine Carlisle.
An Analysis of Hepatitis-C-Positive Liver Donors in the Era of Direct Acting Antiviral Therapies.
Degree: Doctor of Medicine, 2018, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41973520
► TITLE: An Analysis of Hepatitis-C-Positive Liver Donors in the Era of Direct Acting Antiviral Therapies Purpose: To determine whether the recent development of direct acting…
(more)
▼ TITLE: An Analysis of Hepatitis-C-Positive Liver Donors in the Era of Direct Acting Antiviral Therapies
Purpose: To determine whether the recent development of direct acting antiviral drugs (DAAs) has spurred an increase in the transplantation of livers from donors with hepatitis c virus (HCV) and to establish what percent of these livers come from donors with current versus cleared infection using NAT status.
Methods: We retrospectively reviewed data from the United Network for Organ Sharing (UNOS) on all donors, wait-listed candidates and transplant recipients of livers, kidneys, hearts, lungs, intestines and pancreases in the United States from January 2009-March 2016. Data was analyzed using VirtualBox and SAS Studio.
Results: Between 2009 and 2015, less than 5% of all liver transplants came from HCV-positive donors. However the number of HCV-positive livers used for transplant increased, particularly in 2013, when interferon-free DAAs were introduced. Most of these HCV-positive livers were transplanted into HCV-positive recipients (in 2015, 381 went to positive recipients compared to 12 to HCV-negative recipients) and the number of these D-positive/R-positive transplants increased since 2013. In terms of HCV-negative liver donors, more than half were transplanted into HCV-negative recipients, and the number transplanted into HCV-positive recipients decreased from 2014-15. This suggests an increasing propensity to give HCV-positive recipients an HCV-positive liver when previously more of those donations were discarded. Wait-list data showed that while HCV-positive recipients experience longer wait times for liver transplants compared to HCV-negative recipients, the disparity in wait times has decreased by more than 50% from 2000 to 2015. In terms of NAT status, of all organ donors (including heart, lung, liver, kidney, intestine, pancreas) evaluated for transplant between January 2015 and March 2016 that were HCV-antibody positive, two-thirds were also NAT-positive and one third were NAT-negative, reflecting current and cleared infection states, respectively.
Conclusions: Our data indicate that the development of IFN-free DAAs has prompted increased usage of HCV-positive livers for transplantation, resulting in shorter wait times for all recipients. Thus enhanced use of HCV-positive donor organs offers hope for optimal organ utilization of a previously high-risk donor pool.
Scholarly Project
Subjects/Keywords: HCV; transplantation; UNOS; liver
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Stoeckle, C. C. (2018). An Analysis of Hepatitis-C-Positive Liver Donors in the Era of Direct Acting Antiviral Therapies. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:41973520
Chicago Manual of Style (16th Edition):
Stoeckle, Catherine Carlisle. “An Analysis of Hepatitis-C-Positive Liver Donors in the Era of Direct Acting Antiviral Therapies.” 2018. Doctoral Dissertation, Harvard University. Accessed March 04, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41973520.
MLA Handbook (7th Edition):
Stoeckle, Catherine Carlisle. “An Analysis of Hepatitis-C-Positive Liver Donors in the Era of Direct Acting Antiviral Therapies.” 2018. Web. 04 Mar 2021.
Vancouver:
Stoeckle CC. An Analysis of Hepatitis-C-Positive Liver Donors in the Era of Direct Acting Antiviral Therapies. [Internet] [Doctoral dissertation]. Harvard University; 2018. [cited 2021 Mar 04].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41973520.
Council of Science Editors:
Stoeckle CC. An Analysis of Hepatitis-C-Positive Liver Donors in the Era of Direct Acting Antiviral Therapies. [Doctoral Dissertation]. Harvard University; 2018. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41973520
Duquesne University
23.
Schrott, Valerie.
Characterization of the Hepatitis C Virus Genome Interactions with the microRNA miR-122: Potential New Therapeutic Targets for Peptide Nucleic Acid Based Strategies.
Degree: MS, Chemistry and Biochemistry, 2012, Duquesne University
URL: https://dsc.duq.edu/etd/1157
► Hepatitis C virus (HCV), a positive-sense RNA virus that chronically infects between 2.7 and 3.9 million Americans, is highly mutational, making the HCV infection difficult…
(more)
▼ Hepatitis C virus (
HCV), a positive-sense RNA virus that chronically infects between 2.7 and 3.9 million Americans, is highly mutational, making the
HCV infection difficult to treat. Thus, it is of high interest to search for highly conserved therapeutic targets within the
HCV genome. Two such sequences are located within the 5' untranslated region (UTR) of
HCV, being complementary for the microRNA miR-122, a liver microRNA essential for the production of the infectious virus. The use of peptide nucleic acids (PNAs) as therapeutic agents has become a promising area of study in recent years. In this study, we characterized the interactions between miR-122 and the
HCV 5'UTR and designed PNAs to disrupt these interactions and thus, inhibit RNA replication and translation. Our results show that the PNAs effectively disrupt the interactions involving miR-122 and the 5'UTR, thereby increasing the possibility of a new therapeutic option against
HCV.
Advisors/Committee Members: Mihaela-Rita Mihailescu, Michael Cascio, Ellen Gawalt.
Subjects/Keywords: HCV; miR-122; PNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Schrott, V. (2012). Characterization of the Hepatitis C Virus Genome Interactions with the microRNA miR-122: Potential New Therapeutic Targets for Peptide Nucleic Acid Based Strategies. (Masters Thesis). Duquesne University. Retrieved from https://dsc.duq.edu/etd/1157
Chicago Manual of Style (16th Edition):
Schrott, Valerie. “Characterization of the Hepatitis C Virus Genome Interactions with the microRNA miR-122: Potential New Therapeutic Targets for Peptide Nucleic Acid Based Strategies.” 2012. Masters Thesis, Duquesne University. Accessed March 04, 2021.
https://dsc.duq.edu/etd/1157.
MLA Handbook (7th Edition):
Schrott, Valerie. “Characterization of the Hepatitis C Virus Genome Interactions with the microRNA miR-122: Potential New Therapeutic Targets for Peptide Nucleic Acid Based Strategies.” 2012. Web. 04 Mar 2021.
Vancouver:
Schrott V. Characterization of the Hepatitis C Virus Genome Interactions with the microRNA miR-122: Potential New Therapeutic Targets for Peptide Nucleic Acid Based Strategies. [Internet] [Masters thesis]. Duquesne University; 2012. [cited 2021 Mar 04].
Available from: https://dsc.duq.edu/etd/1157.
Council of Science Editors:
Schrott V. Characterization of the Hepatitis C Virus Genome Interactions with the microRNA miR-122: Potential New Therapeutic Targets for Peptide Nucleic Acid Based Strategies. [Masters Thesis]. Duquesne University; 2012. Available from: https://dsc.duq.edu/etd/1157
University of New South Wales
24.
Baharuddin, Benny.
Metabolic dysfunction in T cells during hepatitis C virus infection.
Degree: Medical Sciences, 2015, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/55779
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:39271/SOURCE02?view=true
► T cell glucose metabolism is essential for the provision of energy to sustain and maintain T cell function, the so called, fuel for energy. In…
(more)
▼ T cell glucose metabolism is essential for the provision of energy to sustain and maintain T cell function, the so called, fuel for energy. In hepatitis C virus (
HCV) infection, the immune response is a key determinant to outcome after primary infection, and with antiviral therapy for chronic
HCV infection. The overall aim of this thesis was to examine T cell glucose metabolism in
HCV infection and its association with T cell responses in chronic and primary
HCV infection. To achieve this, key markers of glucose metabolism and T cell activation were studied in individuals with chronic
HCV infection prior to receiving antiviral therapy and prior to primary infection.This is the first study to report that patients with chronic
HCV infection demonstrate impaired glucose metabolism in both CD8 and CD4 T cells. Further, patients with chronic
HCV infection who achieved viral clearance with PegIFN therapy, glucose metabolism as assessed by pAkt and glucose uptake, recovered to levels of healthy subjects. This data indicates dysfunctional T cell glucose metabolism may be a viral driven effect that may impact T cell function and viral clearance.Interestingly, low pAkt level was associated with reduced T cell activation markers (measured by CD25 and PD1) in both CD8 and CD4 T cells and their antigen-experienced subpopulations. Further, reduced pAkt level and T cell activation was associated with impaired production of effector antiviral cytokines in treatment non-responders. Lastly, non-responders had reduced frequency of terminally differentiated, effector and central memory T cells. The results from this study suggest that impaired T cell glucose metabolism, may affect T cell activation, function, effector phenotype differentiation and treatment outcome.Finally, the role of host related factors in potentially influencing the observed dysfunction in T cell glucose metabolism was further studied in individuals prior to primary
HCV infection, and with known outcome from infection (spontaneous clearing versus chronic infection). The studies did not show any differences between the two groups before infection in terms of pAkt or glucose metabolism. Further, known SNPs within the Akt gene was not predictive of outcome of primary
HCV infection. Thus, thexxresults suggest that pre-existent host factors related to Akt does not predict acute
HCV infection outcome.The data from this thesis indicate that
HCV infection is associated with dysfunctional T cell glucose metabolism which may impact T cell activation, differentiation and the response to antiviral therapy. These studies are the first to report impaired T cell glucose metabolism during chronic
HCV infection and improved our understanding of the relationship of
HCV and T cell function.
Advisors/Committee Members: Zekry, Amany, Clinical School - St George Hospital, Faculty of Medicine, UNSW, Simar, David, Medical Sciences, Faculty of Medicine, UNSW.
Subjects/Keywords: metabolism; HCV; T cell
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Baharuddin, B. (2015). Metabolic dysfunction in T cells during hepatitis C virus infection. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/55779 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:39271/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Baharuddin, Benny. “Metabolic dysfunction in T cells during hepatitis C virus infection.” 2015. Doctoral Dissertation, University of New South Wales. Accessed March 04, 2021.
http://handle.unsw.edu.au/1959.4/55779 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:39271/SOURCE02?view=true.
MLA Handbook (7th Edition):
Baharuddin, Benny. “Metabolic dysfunction in T cells during hepatitis C virus infection.” 2015. Web. 04 Mar 2021.
Vancouver:
Baharuddin B. Metabolic dysfunction in T cells during hepatitis C virus infection. [Internet] [Doctoral dissertation]. University of New South Wales; 2015. [cited 2021 Mar 04].
Available from: http://handle.unsw.edu.au/1959.4/55779 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:39271/SOURCE02?view=true.
Council of Science Editors:
Baharuddin B. Metabolic dysfunction in T cells during hepatitis C virus infection. [Doctoral Dissertation]. University of New South Wales; 2015. Available from: http://handle.unsw.edu.au/1959.4/55779 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:39271/SOURCE02?view=true
University of New South Wales
25.
Bretana, Neil.
Understanding the dynamics of hepatitis C virus transmission in a high-risk environment.
Degree: Medical Sciences, 2017, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/57161
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42740/SOURCE02?view=true
► HCV is mainly transmitted between people who inject drugs in developed countries. In this population, HCV prevalence is high and incarceration is recognised to be…
(more)
▼ HCV is mainly transmitted between people who inject drugs in developed countries. In this population,
HCV prevalence is high and incarceration is recognised to be an independent risk factor for infection. This thesis integrates epidemiology, molecular epidemiology, and computational modelling to investigate
HCV transmission among inmates in NSW prisons.In the first study,
HCV incidence and associated risk behaviours were calculated in a prospective cohort of inmates in NSW prisons. Thirty-eight
HCV incident cases were identified in 269.94 person-years of follow-up yielding an estimated
HCV incidence of 14.08 (95% CI: 9.96-19.32) per 100 person-years. Indigenous identity, injecting daily or more often, and injecting heroin were found to be associated with an increased risk of
HCV infection.The second study integrated virus sequences with risk behaviour and spatio-temporal data in order to reveal transmission clusters among inmates in NSW. Three clusters of recent
HCV transmission were detected consisting of four in-custody transmission events involving drug injecting and sharing between source/recipient pairs located in the same prison at the same time. Despite a large background population of prisoners with chronic
HCV, transmission events from recently infected individuals were identified in the prison setting. In the third study, a computational model was developed to simulate the ongoing
HCV epidemics in the NSW prisons. The model was used to predict future epidemiological trends and investigate scenarios of altered risk affecting the epidemic. The projected incidence of
HCV was stable at 9.72 (95% CI: 9.36-10.08) per 100 person-years until 2020. The potential impact of changes in incarceration rates, and
HCV prevention strategies to reduce
HCV transmission in NSW prisons were explored. This approach of integrated epidemiological, molecular epidemiological and modeling methods to study
HCV transmissions has clear capacity to inform policy and public health practice in the prison setting. Future work includes consideration of social network information, assessment of new antiviral treatment strategies in NSW prisons, and enhancing linkage with community-based research.
Advisors/Committee Members: Luciani, Fabio, Medical Sciences, Faculty of Medicine, UNSW, Lloyd, Andrew, Medical Sciences, Faculty of Medicine, UNSW, Bull, Rowena, Medical Sciences, Faculty of Medicine, UNSW, Betz-Stablein, Brigid, Medical Sciences, Faculty of Medicine, UNSW.
Subjects/Keywords: Prison; HCV; Transmission; Model; Phylogenetics
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bretana, N. (2017). Understanding the dynamics of hepatitis C virus transmission in a high-risk environment. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/57161 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42740/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Bretana, Neil. “Understanding the dynamics of hepatitis C virus transmission in a high-risk environment.” 2017. Doctoral Dissertation, University of New South Wales. Accessed March 04, 2021.
http://handle.unsw.edu.au/1959.4/57161 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42740/SOURCE02?view=true.
MLA Handbook (7th Edition):
Bretana, Neil. “Understanding the dynamics of hepatitis C virus transmission in a high-risk environment.” 2017. Web. 04 Mar 2021.
Vancouver:
Bretana N. Understanding the dynamics of hepatitis C virus transmission in a high-risk environment. [Internet] [Doctoral dissertation]. University of New South Wales; 2017. [cited 2021 Mar 04].
Available from: http://handle.unsw.edu.au/1959.4/57161 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42740/SOURCE02?view=true.
Council of Science Editors:
Bretana N. Understanding the dynamics of hepatitis C virus transmission in a high-risk environment. [Doctoral Dissertation]. University of New South Wales; 2017. Available from: http://handle.unsw.edu.au/1959.4/57161 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42740/SOURCE02?view=true
University of New South Wales
26.
Cunningham, Evan.
Transmission and treatment of hepatitis C virus infection in people who inject drugs.
Degree: Kirby Institute, 2017, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/58947
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48008/SOURCE02?view=true
► Background: The advent of novel, highly efficacious, and well tolerated hepatitis C virus (HCV) therapies could potentially lead to the elimination of HCV in many…
(more)
▼ Background: The advent of novel, highly efficacious, and well tolerated hepatitis C virus (
HCV) therapies could potentially lead to the elimination of
HCV in many settings globally. A better understanding of
HCV transmission and treatment among people who inject drugs (PWID) is needed for this potential to be realised. Aims: The broad aim of this research was to inform prevention and treatment of
HCV infection in PWID. Specific aims included the evaluation of injecting risk behaviours and incidence of
HCV infection among PWID in an Australian prison setting; to investigate
HCV transmission via phylogenetic analyses in a population of street-involved youth in Vancouver, Canada; and to evaluate adherence to pegylated interferon/ribavirin therapy and sofosbuvir/velpatasvir therapy among PWID.Methods: In Chapter 2 and Chapter 3, data from the HITS-p study were analysed using Cox proportional hazard, logistic regression, and generalized estimating equation (GEE) methodologies. In Chapter 4, data from the At-Risk Youth Study (ARYS) were analysed using maximum likelihood phylogenetic and logistic regression methods. In Chapter 5 and 6, adherence and behavioural data from the ACTIVATE and SIMPLIFY studies were analysed using GEE and logistic regression methodologies. Key findings: In the HITS-p study, primary
HCV infection was associated with needle/syringe sharing irrespective of injecting frequency or drug type. The incidence was high and remained stable between 2005 and 2014. Needle/syringe sharing increased following entry into prison while any injecting drug use decreased. Younger age was associated with continuing and reinitiating injecting following prison entry as well as ongoing injecting risk behaviours while in prison. Methamphetamine injecting was associated with phylogenetic clustering in street-involved youth. PWID demonstrated high adherence to both PEG-IFN/RBV and sofosbuvir/velpatasvir. Injecting cocaine or amphetamines was associated with reduced adherence to sofosbuvir/velpatasvir however any injecting at baseline was not associated with overall adherence to therapy.Conclusion: A multifaceted approach is needed to effectively reduce the prevalence and incidence of
HCV infection among PWID. Scale up of
HCV prevention strategies including needle and syringe programs and opioid substitution therapy are needed to supplement the scale up of DAA therapy to provide the greatest prevention benefit to meet global
HCV elimination targets.
Advisors/Committee Members: Grebely, Jason, Kirby Institute, Faculty of Medicine, UNSW, Applegate, Tanya, Kirby Institute, Faculty of Medicine, UNSW, Hajarizadeh, Behzad, Kirby Institute, Faculty of Medicine, UNSW, Dore, Gregory, Kirby Institute, Faculty of Medicine, UNSW, Lloyd, Andrew, Kirby Institute, Faculty of Medicine, UNSW.
Subjects/Keywords: Epidemiology; HCV; PWID; DAA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cunningham, E. (2017). Transmission and treatment of hepatitis C virus infection in people who inject drugs. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/58947 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48008/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Cunningham, Evan. “Transmission and treatment of hepatitis C virus infection in people who inject drugs.” 2017. Doctoral Dissertation, University of New South Wales. Accessed March 04, 2021.
http://handle.unsw.edu.au/1959.4/58947 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48008/SOURCE02?view=true.
MLA Handbook (7th Edition):
Cunningham, Evan. “Transmission and treatment of hepatitis C virus infection in people who inject drugs.” 2017. Web. 04 Mar 2021.
Vancouver:
Cunningham E. Transmission and treatment of hepatitis C virus infection in people who inject drugs. [Internet] [Doctoral dissertation]. University of New South Wales; 2017. [cited 2021 Mar 04].
Available from: http://handle.unsw.edu.au/1959.4/58947 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48008/SOURCE02?view=true.
Council of Science Editors:
Cunningham E. Transmission and treatment of hepatitis C virus infection in people who inject drugs. [Doctoral Dissertation]. University of New South Wales; 2017. Available from: http://handle.unsw.edu.au/1959.4/58947 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48008/SOURCE02?view=true
University of Sydney
27.
Najim, Mustafa.
Hepatitis C virus induced changes in cellular trafficking and lipid metabolism - identifying novel host factors required for HCV replication
.
Degree: 2018, University of Sydney
URL: http://hdl.handle.net/2123/20895
► Hepatitis C virus (HCV) infection is endemic in numerous countries and is a global health issue, placing a huge burden on health care systems and…
(more)
▼ Hepatitis C virus (HCV) infection is endemic in numerous countries and is a global health issue, placing a huge burden on health care systems and society. The high prevalence of people who are chronically infected with HCV, the disease burden and the absence of an effective vaccine reinforce the importance of HCV treatment in controlling this disease. Direct acting antivirals (DAAs), have revolutionised HCV treatment over the last few years. However, people failing DAAs typically develop antiviral resistance, so new treatments may still be needed in future. To identify novel host factors involved in HCV infection, a mass spectrometry based Stable Isotope Labelling of Amino acids in Cell culture (SILAC) screen was performed, to identify proteins that are enriched in the Endoplasmic Reticulum (ER) of HCV infected hepatocytes. This showed significant upregulation of Coatomer Protein Complex-I (COPI). Next, we examined the effect of Phosphatidylinositol 4-phosphate (PI4P) depletion on tafficking of COPI to the ER and on HCV replication, by over-expressing the PI4P phosphatase Sac1. However, due to the limitations of the model, we could neither prove or disprove this hypothesis, as we could not achieve sustained overexpression of Sac1. Next, we evaluated the consequence of silencing heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNPC1/C2) and transmembrane 6 superfamily member 2 (TM6SF2) on HCV replication. We found that hnRNPC1/C2 inhibition has no effect on HCV replication, while TM6SF2 is required for HCV replication. In summary, these findings identify a range of essential host proteins that could be targeted by novel host-targeting antiviral drugs. Finally, our findings provide potential insights into the life cycle of other related viruses, which have far fewer treatments available.
Subjects/Keywords: HCV;
TM6SF2;
hnRNPC1/C2;
COPI
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Najim, M. (2018). Hepatitis C virus induced changes in cellular trafficking and lipid metabolism - identifying novel host factors required for HCV replication
. (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/20895
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Najim, Mustafa. “Hepatitis C virus induced changes in cellular trafficking and lipid metabolism - identifying novel host factors required for HCV replication
.” 2018. Thesis, University of Sydney. Accessed March 04, 2021.
http://hdl.handle.net/2123/20895.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Najim, Mustafa. “Hepatitis C virus induced changes in cellular trafficking and lipid metabolism - identifying novel host factors required for HCV replication
.” 2018. Web. 04 Mar 2021.
Vancouver:
Najim M. Hepatitis C virus induced changes in cellular trafficking and lipid metabolism - identifying novel host factors required for HCV replication
. [Internet] [Thesis]. University of Sydney; 2018. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2123/20895.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Najim M. Hepatitis C virus induced changes in cellular trafficking and lipid metabolism - identifying novel host factors required for HCV replication
. [Thesis]. University of Sydney; 2018. Available from: http://hdl.handle.net/2123/20895
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University College London (University of London)
28.
Whitby, Kevin Peter.
The development and application of quantitative PCR-based assays for the detection of hepatitis C and related viruses.
Degree: PhD, 1999, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/10119697/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313529
► PCR has previously been used to measure hepatitis C virus (HCV) levels during antiviral chemotherapy, in viral cultures and in diverse clinical samples. The use…
(more)
▼ PCR has previously been used to measure hepatitis C virus (HCV) levels during antiviral chemotherapy, in viral cultures and in diverse clinical samples. The use of this technique led to a rapid expansion of our understanding of this clinically important virus. However, the majority of methods previously used to quantify HCV were laborious and relatively insensitive. This thesis describes the development of PCR-based quantitative methods for HCV RNA and their application in a number of research settings. Significant advances in assay speed and throughput are demonstrated, as well as important improvements in sensitivity. The aim of the project was to develop and optimise quantitative PCR methods which could conveniently be applied to serum or plasma and also to cells and cell culture supernatants from in vitro culture experiments. The PCR method developed was shown to be effective in providing quantitative viral monitoring data from several trials of antiviral chemotherapy. Viral RNA levels were also monitored in the serum of a patient infected during pregnancy, in a cultured hepatocyte line and the method was also applied to the study of a potential small primate model. The quantity of virus in cultured hepatocytes and in plasma pools prior to fractionation was demonstrated to be very low. In addition a novel single tube 'hot-start' RT-PCR method (RT-HS-PCR) is described. This method was shown to increase the sensitivity of RT-PCR and to provide quantitative data. The discovery of a new flavivirus (GBV-C), closely related to HCV, provided an opportunity to demonstrate the flexibility of this quantitative PCR method. The technique has now been applied to a wide range of DNA and RNA viruses in several laboratories within the UK.
Subjects/Keywords: 579; HCV
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Whitby, K. P. (1999). The development and application of quantitative PCR-based assays for the detection of hepatitis C and related viruses. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/10119697/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313529
Chicago Manual of Style (16th Edition):
Whitby, Kevin Peter. “The development and application of quantitative PCR-based assays for the detection of hepatitis C and related viruses.” 1999. Doctoral Dissertation, University College London (University of London). Accessed March 04, 2021.
https://discovery.ucl.ac.uk/id/eprint/10119697/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313529.
MLA Handbook (7th Edition):
Whitby, Kevin Peter. “The development and application of quantitative PCR-based assays for the detection of hepatitis C and related viruses.” 1999. Web. 04 Mar 2021.
Vancouver:
Whitby KP. The development and application of quantitative PCR-based assays for the detection of hepatitis C and related viruses. [Internet] [Doctoral dissertation]. University College London (University of London); 1999. [cited 2021 Mar 04].
Available from: https://discovery.ucl.ac.uk/id/eprint/10119697/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313529.
Council of Science Editors:
Whitby KP. The development and application of quantitative PCR-based assays for the detection of hepatitis C and related viruses. [Doctoral Dissertation]. University College London (University of London); 1999. Available from: https://discovery.ucl.ac.uk/id/eprint/10119697/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313529
University of Sydney
29.
Selvamani, Sakthi.
Effect of Hepatitis B and C Viruses on Mitochondrial Function
.
Degree: 2020, University of Sydney
URL: http://hdl.handle.net/2123/24376
► HCV and HBV infections are leading causes of chronic hepatitis, cirrhosis, and hepatocellular carcinoma and can induce metabolic dysfunction, which may offer a selective advantage…
(more)
▼ HCV and HBV infections are leading causes of chronic hepatitis, cirrhosis, and hepatocellular carcinoma and can induce metabolic dysfunction, which may offer a selective advantage for liver cancer proliferation and survival. The liver is enriched with numerous mitochondria, providing a continuous supply of ATP for a range of cellular activities. The hypothesis of this thesis is that HBV and HCV induce mitochondrial dysfunction and metabolic disorders. A range of cell culture models and in vitro techniques were used to test this hypothesis, including the Seahorse analyser to measure mitochondrial function in real time. Mitochondrial function and membrane potential during HCV and HBV infection were decreased, which were independent of mitochondrial biogenesis. HCV infection promotes steatosis due to a combination of viral and host metabolic factors, whereas steatosis during HBV is more variable. Therefore, potential changes in lipid metabolism were investigated in our HCV and HBV models. Impaired lipid oxidation was observed during HCV infection, but not during HBV expression. Perturbation of pyruvate metabolism was proposed as a possible mechanism for mitochondrial dysfunction during HBV expression. No significant change in pyruvate but an increase in lactate concentrations was observed, due to elevated lactate dehydrogenase A, which converts pyruvate to lactate. Proteomics analysis revealed other key proteins involved in pyruvate metabolism to be differentially regulated, including increased levels of pyruvate dehydrogenase kinase. In summary, HCV infection causes mitochondrial dysfunction and reduced lipid oxidation, resulting in intracellular accumulation of lipids. In contrast, HBV expression does not affect lipids but alters pyruvate metabolism, causing lactate accumulation and promoting the “Warburg effect”. Thus, although HBV does not cause steatosis, the lactate accumulation and altered cell metabolism may promote the development and progression of liver cancer.
Subjects/Keywords: HBV;
HCV;
Mitochondria;
steatosis;
ATP
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Selvamani, S. (2020). Effect of Hepatitis B and C Viruses on Mitochondrial Function
. (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/24376
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Selvamani, Sakthi. “Effect of Hepatitis B and C Viruses on Mitochondrial Function
.” 2020. Thesis, University of Sydney. Accessed March 04, 2021.
http://hdl.handle.net/2123/24376.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Selvamani, Sakthi. “Effect of Hepatitis B and C Viruses on Mitochondrial Function
.” 2020. Web. 04 Mar 2021.
Vancouver:
Selvamani S. Effect of Hepatitis B and C Viruses on Mitochondrial Function
. [Internet] [Thesis]. University of Sydney; 2020. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2123/24376.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Selvamani S. Effect of Hepatitis B and C Viruses on Mitochondrial Function
. [Thesis]. University of Sydney; 2020. Available from: http://hdl.handle.net/2123/24376
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Indian Institute of Science
30.
Kumar, Anuj.
Mechanistic Insights into Translation and Replication of Hepatitis C Virus RNA : Exploring Direct-Acting Antivirals.
Degree: PhD, Faculty of Science, 2018, Indian Institute of Science
URL: http://etd.iisc.ac.in/handle/2005/3260
► Hepatitis C virus (HCV), a blood-borne pathogen, is a small enveloped RNA virus belonging to the Hepacivirus genus of the Flaviviridae family. HCV infection represents…
(more)
▼ Hepatitis C virus (
HCV), a blood-borne pathogen, is a small enveloped RNA virus belonging to the Hepacivirus genus of the Flaviviridae family.
HCV infection represents one of the major health concerns affecting approximately 170 million people globally. Patients with chronic
HCV infection are at risk of developing hepatic fibrosis, cirrhosis and hepatocellular carcinoma. No protective anti-
HCV vaccine is available yet. Until recently, standard therapy based on pegylated interferon plus ribavirin, was inadequate in treating all the patients as it results in a sustained virological response in only 40 to 50 percent of patients infected with the most common genotype (gt 1). Advances in understanding host-
HCV interactions have helped developing newer anti-
HCV agents such as telaprevir and boceprevir. However, treatment success is still limited due to different factors including genotype specificity, high cost, potential drug-drug interactions, substantial side effects etc.
The positive-sense single-stranded RNA genome of
HCV is approximately 9.6kb long which is flanked by highly structured and conserved 5’ and 3’ untranslated regions (UTRs) at both ends. Unlike cap-dependent translation of host cell mRNAs,
HCV translation is mediated by an internal ribosomal entry site (IRES) present majorly within the 5’UTR. Several reports have demonstrated the interaction of different cellular proteins with
HCV-5’UTR and/or 3’UTR, which include human La protein, polypyrimidine tract binding protein (PTB), poly (rC)-binding protein 2 (PCBP2) etc. These interactions of trans-acting factors with the UTRs may be important for
HCV translation and/or replication. Earlier study from our laboratory revealed the importance of interaction of human La protein, by its central RNA recognition motif (RRM), with the
HCV IRES around a tetranucleotide sequence GCAC near initiator AUG in influencing
HCV translation. However, the role of this interaction, if any, in
HCV RNA replication was not known. In the first part of the thesis, we characterized the interaction between human La protein and the GCAC to understand its role in
HCV replication. We incorporated mutation, which altered the binding of La, in the GCAC motif in
HCV monocistronic replicon and checked
HCV RNA replication by reverse transcriptase polymerase chain reaction (RT-PCR). The mutation drastically inhibited
HCV replication. Interestingly, overexpression of La could reverse the effect of this mutation and significantly enhanced
HCV RNA levels. Using a bicistronic replicon, we observed that decrease in replication was independent of translation inhibition. Furthermore, mutation at the GCAC motif reduced the association between La and viral polymerase, NS5B as seen in co-immunoprecipitation assays. Moreover, this mutation affected translation to replication switch regulated by the interplay between
HCV-NS3 protease and human La protein. Our analyses of point mutations, based on RT-PCR and luciferase assays, revealed distinct roles of each nucleotide of the GCAC motif in
HCV replication…
Advisors/Committee Members: Das, Saumitra (advisor).
Subjects/Keywords: Hepatitis C Virus RNA; HCV Genotypes; HCV Vaccines; Hepatitis C Virus Infection; Antivirals; Human La Protein; Hepatitis C Virus Life Cycle; Viral Proteins; HCV Replication; HCV IRES; HCV Translation; HCV Infection; HCV Vaccine Development; Hepatitis C Virus (HCV); Microbiology and Cell Biology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kumar, A. (2018). Mechanistic Insights into Translation and Replication of Hepatitis C Virus RNA : Exploring Direct-Acting Antivirals. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/3260
Chicago Manual of Style (16th Edition):
Kumar, Anuj. “Mechanistic Insights into Translation and Replication of Hepatitis C Virus RNA : Exploring Direct-Acting Antivirals.” 2018. Doctoral Dissertation, Indian Institute of Science. Accessed March 04, 2021.
http://etd.iisc.ac.in/handle/2005/3260.
MLA Handbook (7th Edition):
Kumar, Anuj. “Mechanistic Insights into Translation and Replication of Hepatitis C Virus RNA : Exploring Direct-Acting Antivirals.” 2018. Web. 04 Mar 2021.
Vancouver:
Kumar A. Mechanistic Insights into Translation and Replication of Hepatitis C Virus RNA : Exploring Direct-Acting Antivirals. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2018. [cited 2021 Mar 04].
Available from: http://etd.iisc.ac.in/handle/2005/3260.
Council of Science Editors:
Kumar A. Mechanistic Insights into Translation and Replication of Hepatitis C Virus RNA : Exploring Direct-Acting Antivirals. [Doctoral Dissertation]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/3260
◁ [1] [2] [3] [4] [5] … [14] ▶
. 
Open Access Theses and Dissertations