subject:(hepatitis C virus)

Rutgers University

1. Wang, Yuanyuan, 1991-. Overcoming challenges on HCV glycoproteins and receptors production: a useful mammalian cell expression system.

Degree: PhD, Chemistry and Chemical Biology, 2019, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/60087/

►

Hepatitis C is a liver disease caused by hepatitis C virus (HCV). HCV is the major cause of cirrhosis and hepatocellular cancer in the US… (more)

▼

Hepatitis C is a liver disease caused by hepatitis C virus (HCV). HCV is the major cause of cirrhosis and hepatocellular cancer in the US and is the number one cause of liver transplantation. An estimate of 3.5 million people is chronically infected in the US with 400,000 individuals deaths from chronic HCV infection every year. Several direct-acting antiviral (DAA) agents have been approved by the Food and Drug Administration (FDA). HCV is a blood-borne virus, which prior to 1992 was transmitted through blood transfusion. An estimated 41,200 new cases of HCV infection occurred in the US with an additional 1.75 million worldwide in 2016. Therefore, there is an urgent need to control the transmission of HCV, in addition to the antiviral intervention to limit the spread of the virus. Vaccination is the most effective way to control the infection rate as no infectious disease has ever been eradicated by treatment alone. However, no vaccine is available to prevent HCV infection. A useful mammalian cell expression system was described to produce HCV envelope glycoproteins E1 and E2, as well as the cell surface receptors, scavenger receptor class B type I (SRB1) and cluster of differentiation 81 (CD81). Our method combines the speed and high efficiency of lentiviral infection with an adherent cell bioreactor to allow large-scale production of proteins in mammalian cell lines. The full-length ectodomain of HCV E1 was produced at milligram quantity and is recognized by conformational antibodies from patient samples. E1 can associate with the apolipoproteins from the cell culture serum. HCV E2 produced by the mammalian cell expression system has the function to bind cell surface receptors and antibodies. Crystals of E2 and CD81 diffract to 4.3 Å resolution allowing us to produce a low-resolution model of the E2-receptor complex. Overall, our result extends the current understanding of HCV entry by providing more structural, biophysical, and functional information on the HCV glycoproteins. The studies of the receptor interaction can contribute to vaccine design to halt the spread of HCV infection.

Advisors/Committee Members: Marcotrigiano, Joseph (chair), Case, David (internal member), Baum, Jean (internal member), Arnold, Eddy (internal member), Cohen, Jeffrey (outside member), School of Graduate Studies.

Subjects/Keywords: Hepatitis C virus – Treatment

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, Yuanyuan, 1. (2019). Overcoming challenges on HCV glycoproteins and receptors production: a useful mammalian cell expression system. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/60087/

Chicago Manual of Style (16^th Edition):

Wang, Yuanyuan, 1991-. “Overcoming challenges on HCV glycoproteins and receptors production: a useful mammalian cell expression system.” 2019. Doctoral Dissertation, Rutgers University. Accessed January 17, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/60087/.

MLA Handbook (7^th Edition):

Wang, Yuanyuan, 1991-. “Overcoming challenges on HCV glycoproteins and receptors production: a useful mammalian cell expression system.” 2019. Web. 17 Jan 2021.

Vancouver:

Wang, Yuanyuan 1. Overcoming challenges on HCV glycoproteins and receptors production: a useful mammalian cell expression system. [Internet] [Doctoral dissertation]. Rutgers University; 2019. [cited 2021 Jan 17]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60087/.

Council of Science Editors:

Wang, Yuanyuan 1. Overcoming challenges on HCV glycoproteins and receptors production: a useful mammalian cell expression system. [Doctoral Dissertation]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60087/

University of KwaZulu-Natal

2. Shunmugam, Letitia. In silico investigation of hepatitis c virus: a novel perspective into targeted viral inhibition of NS3 helicase, NS 3/4a protease and NS5b RNA dependent RNA polymerase.

Degree: 2019, University of KwaZulu-Natal

URL: https://researchspace.ukzn.ac.za/handle/10413/16623

► Hepatitis C Virus (HCV) is an escalating global healthcare and economic burden that requires extensive intervention to alleviate its control. Over the years, drug design… (more)

▼ Hepatitis C Virus (HCV) is an escalating global healthcare and economic burden that requires extensive intervention to alleviate its control. Over the years, drug design efforts have produced many anti-HCV drugs; however, due to drug resistance brought on by numerous genetic variations of the virus and lack of specificity and stability, current drugs are rendered ineffective. The situation has been further intensified by the absence of a viable vaccine. For these reasons, continuous HCV research is imperative for the design and development of promising inhibitors that address the challenges faced by present antiviral therapies. Moreover, exposure of previously neglected viral protein targets can offer another potentially valuable therapeutic route in drug design research. Structure-based drug design approaches accentuate the development of small inhibitor molecules that interact with therapeutic targets through non-covalent interactions. The unexpected discovery of covalent inhibitors and their distinctive nature of instigating complete and irreversible inhibition of targets have shifted attention away from the use of non-covalent drugs in antiviral treatment. This has led to significant progress in understanding covalent inhibition regarding their underlying mechanism of action and in the design of novel covalent inhibitors that work against biological targets. However, due to difficulties arising in its application and resultant safety, the pharmaceutical industry were reluctant to pursue this strategy. With the use of rational drug design, a novel strategy was then proposed known as selective covalent inhibition. Due to the lack of competent protocols and information, little is known regarding selective covalent inhibition This study investigates three biological HCV targets, NS3 protease, RNA helicase and NS5B RNAdependent RNA polymerase. With constantly evolving viruses like HCV, computational methods including molecular modelling and docking, virtual screening and molecular dynamic simulations have allowed chemists to screen millions of compounds to filter out potential lead drugs. These in silico approaches have allowed Computer-Aided Drug Design as a cost-effective strategy to accelerate the process of drug discovery. The above techniques, with numerous other computational tools were employed in this study to fill the gap in HCV drug research by providing insights into the structural and dynamic changes that describe the mechanism of selective covalent inhibition and pharmacophoric features that lead to unearthing of potential small inhibitor molecules against Hepatitis C. v The first study (Chapter 4) provides a comprehensive review on HCV NS3/4A protein, current therapies and covalent inhibition as well as introduces a technical guideline that provides a systematic approach for the design and development of potent, selective HCV inhibitors. The second study (Chapter 5) provides a comprehensive understanding concerning the implications of selective covalent inhibition on the… Advisors/Committee Members: Soliman, Mahmoud Elsayed Soliman. (advisor).

Subjects/Keywords: Hepatitis C virus - drug design.; Hepatitis C virus - drug delivery.

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shunmugam, L. (2019). In silico investigation of hepatitis c virus: a novel perspective into targeted viral inhibition of NS3 helicase, NS 3/4a protease and NS5b RNA dependent RNA polymerase. (Thesis). University of KwaZulu-Natal. Retrieved from https://researchspace.ukzn.ac.za/handle/10413/16623

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shunmugam, Letitia. “In silico investigation of hepatitis c virus: a novel perspective into targeted viral inhibition of NS3 helicase, NS 3/4a protease and NS5b RNA dependent RNA polymerase.” 2019. Thesis, University of KwaZulu-Natal. Accessed January 17, 2021. https://researchspace.ukzn.ac.za/handle/10413/16623.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shunmugam, Letitia. “In silico investigation of hepatitis c virus: a novel perspective into targeted viral inhibition of NS3 helicase, NS 3/4a protease and NS5b RNA dependent RNA polymerase.” 2019. Web. 17 Jan 2021.

Vancouver:

Shunmugam L. In silico investigation of hepatitis c virus: a novel perspective into targeted viral inhibition of NS3 helicase, NS 3/4a protease and NS5b RNA dependent RNA polymerase. [Internet] [Thesis]. University of KwaZulu-Natal; 2019. [cited 2021 Jan 17]. Available from: https://researchspace.ukzn.ac.za/handle/10413/16623.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shunmugam L. In silico investigation of hepatitis c virus: a novel perspective into targeted viral inhibition of NS3 helicase, NS 3/4a protease and NS5b RNA dependent RNA polymerase. [Thesis]. University of KwaZulu-Natal; 2019. Available from: https://researchspace.ukzn.ac.za/handle/10413/16623

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

3. Manna, David P. Investigation of the Role of Nonstructural 4B Protein in Hepatitis C Virus Replication Complex Formation and Infectious Virus Production .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12560

► The Hepatitis C Virus (HCV) NS4B protein is one of the least understood viral proteins in terms of contributions to the virus lifecycle. NS4B has… (more)

▼ The Hepatitis C Virus (HCV) NS4B protein is one of the least understood viral proteins in terms of contributions to the virus lifecycle. NS4B has many functions related to formation and function of the viral genome replication complex (RC), most notably for its role in inducing a novel membrane structure termed the membranous web which houses the RC. The membranous web is largely believed to be derived from ER membranes, and recent data has also suggested membranes from the early endosome (EE) compartment are part of this membrane structure. This was due to the observation that Rab5, a regulator of EE membrane transport, was required for HCV RNA replication and that Rab5 co-localizes with NS4B foci in replicon cells. NS4B foci are considered to be an immunofluorescence marker equivalent to the membranous web. Recent data has also implicated a new role for the C-terminal domain (CTD) of NS4B in facilitating infectious virus production. Both point mutations and entire CTD sequence swaps between different genotype viruses have highlighted this new and exciting role for NS4B in virus production. To test the hypothesis that cellular Rabs are involved in NS4B-mediated HCV RC formation, we employed two main methods. First, we modified an existing protocol for NS4B antibody directed immunoisolation of a subcellular fraction enriched in the HCV RC components, and used this fraction for immunoblot analysis. Secondly, we examined Rab co-localization with NS4B foci in replicon cells to compare to the profile in the isolated RC fraction, which was competent for HCV RNA synthesis. Rabs from every cellular compartment tested were present at different levels in the isolated RC fraction, but only the endocytic Rab5 and 7 were found to co-localize with NS4B foci. Dominant negative mutants of Rab5 and 7 disrupt NS4B foci, and silencing of Rab5 or 7 resulted in a significant decrease in HCV RNA replication. Taken together, our data implicate endocytic Rabs as being important for NS4B-mediated HCV RC formation. To test the hypothesis that the NS4B CTD is involved in virus assembly, we created chimeric virus genomes where the NS4B CTD from JFH1 virus (genotype 2a, gt2a) was replaced with sequences from Con1 (gt1b) or H77 (gt1a) virus. These chimeric genomes had little impact on RNA replication, but showed a significant defect in virus production, likely at the level of virus assembly. Investigation into the causes of lower virus titers showed that the chimeric viruses have lower NS5A protein levels and a decrease in the NS5A p58/p56 ratio relative to JFH1. Cell culture adapted viruses were generated that had similar titer levels to that of JFH1, showed higher levels of NS5A protein, but interestingly did not change in their NS5A p58/p56 ratio relative to JFH1. Sequencing of the adapted viruses revealed four mutations, two in the chimeric NS4B CTD region, one in domain III of NS5A and one adjacent to the cytosolic loop of the p7 protein. Introduction of these mutations back into the parental chimeric viruses rescued virus production,… Advisors/Committee Members: Kouacou Konan, Dissertation Advisor/Co-Advisor, Kouacou Konan, Committee Chair/Co-Chair, Craig Eugene Cameron, Committee Member, Avery August, Committee Member, Joseph C. Reese, Committee Member, Anthony Paul Schmitt, Committee Member.

Subjects/Keywords: Replication; NS4B; Hepatitis C Virus; Virus production

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Manna, D. P. (2011). Investigation of the Role of Nonstructural 4B Protein in Hepatitis C Virus Replication Complex Formation and Infectious Virus Production . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12560

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Manna, David P. “Investigation of the Role of Nonstructural 4B Protein in Hepatitis C Virus Replication Complex Formation and Infectious Virus Production .” 2011. Thesis, Penn State University. Accessed January 17, 2021. https://submit-etda.libraries.psu.edu/catalog/12560.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Manna, David P. “Investigation of the Role of Nonstructural 4B Protein in Hepatitis C Virus Replication Complex Formation and Infectious Virus Production .” 2011. Web. 17 Jan 2021.

Vancouver:

Manna DP. Investigation of the Role of Nonstructural 4B Protein in Hepatitis C Virus Replication Complex Formation and Infectious Virus Production . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Jan 17]. Available from: https://submit-etda.libraries.psu.edu/catalog/12560.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Manna DP. Investigation of the Role of Nonstructural 4B Protein in Hepatitis C Virus Replication Complex Formation and Infectious Virus Production . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12560

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Indian Institute of Science

4. Bose, Mihika. Characterisation of Monoclonal Antibodies and Small Molecule Inhibitors as Hepatitis C Virus Entry Inhibitors.

Degree: PhD, Faculty of Science, 2017, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/2920

► Hepatitis C virus (HCV) represents a global health threat. HCV is a blood-borne positive-strand RNA virus belonging to the Flaviviridae family that infects ~160 million… (more)

▼ Hepatitis C virus (HCV) represents a global health threat. HCV is a blood-borne positive-strand RNA virus belonging to the Flaviviridae family that infects ~160 million people worldwide. About 70% of infected individuals fail to clear the virus and subsequently develop chronic hepatitis, frequently leading to liver cirrhosis and in some cases hepatocellular carcinoma. Therapeutic options for HCV infection are still limited and a protective vaccine is not yet available. Currently available therapies include administration of pegylated alpha interferon in combination with ribavirin. The recently approved protease inhibitors Boceprevir and Telaprevir are also included in the treatment regimen. However, limitations to the treatment with direct-acting antivirals (DAAs) are associated with severe side effects and low sustained virological response (SVR) rates that vary depending on the virus and host genotype. The replication step of the viral life cycle is mostly targeted by majority of DAAs. Recent findings have suggested that a combination of entry inhibitors together with DAAs exhibit a synergistic effect in the treatment of HCV. Therefore, identification of efficient HCV entry inhibitors is of high priority In vitro studies have shown that HCV attachment and subsequent entry into the host cells is mediated by E1 and E2 viral envelope proteins. HCV entry requires interaction with a number of receptors which include CD81, scavenger receptor B1 (SR-B1) and the tight junction proteins, claudin 1 (CLDN1) and occludin (OCLN). Since the E2 glycoprotein is reported to interact directly with cellular receptors, it is an attractive target for neutralisation. The present study focuses on the establishment and characterisation of entry inhibitors as antivirals for HCV. The thesis is presented in three chapters: Chapter 1- ‘Introduction’, provides a brief overview on HCV genotypes, genome organisation, life cycle including details on the entry process and therapies used for the treatment of HCV. Chapter 2 describes the generation of monoclonal antibodies (mAbs) against HCV envelope proteins as potent anti-viral agents for the prevention of HCV infection. Data on the identification and characterization of the neutralizing epitopes of HCV envelope proteins have been presented. Chapter 3 includes isolation of entry inhibitors of HCV from natural sources and identification and characterization of the active components exhibiting antiviral property. A number of studies have reported the role of neutralizing antibodies in the course of HCV infection and emerging data suggest protective effect of antibodies against HCV infection. Most of the ongoing studies are based on HCV genotype 1a which is prevalent globally. However in India, the prevalent genotype is 3a. Therefore, we established a panel of mAbs against HCV-LPs comprising of core-E1-E2 derived from genotype 3a as described in chapter 2. HCV-LP based system has been used in this study since it mimics the biophysical conformation, morphology and antigenic properties of the native… Advisors/Committee Members: Karande, Anjali A (advisor).

Subjects/Keywords: Hepatitis C Virus; Monoclonal Antibodies; Hepatitis C Virus Infection; Hepatitis C Virus Entry; HCV Small Molecule Inhibitors; Hepatitis C Virus Treatment; HCV Treatment; Rutin; Hepatitis C Virus E2 Protein; Biochemistry

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bose, M. (2017). Characterisation of Monoclonal Antibodies and Small Molecule Inhibitors as Hepatitis C Virus Entry Inhibitors. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/2920

Chicago Manual of Style (16^th Edition):

Bose, Mihika. “Characterisation of Monoclonal Antibodies and Small Molecule Inhibitors as Hepatitis C Virus Entry Inhibitors.” 2017. Doctoral Dissertation, Indian Institute of Science. Accessed January 17, 2021. http://etd.iisc.ac.in/handle/2005/2920.

MLA Handbook (7^th Edition):

Bose, Mihika. “Characterisation of Monoclonal Antibodies and Small Molecule Inhibitors as Hepatitis C Virus Entry Inhibitors.” 2017. Web. 17 Jan 2021.

Vancouver:

Bose M. Characterisation of Monoclonal Antibodies and Small Molecule Inhibitors as Hepatitis C Virus Entry Inhibitors. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2017. [cited 2021 Jan 17]. Available from: http://etd.iisc.ac.in/handle/2005/2920.

Council of Science Editors:

Bose M. Characterisation of Monoclonal Antibodies and Small Molecule Inhibitors as Hepatitis C Virus Entry Inhibitors. [Doctoral Dissertation]. Indian Institute of Science; 2017. Available from: http://etd.iisc.ac.in/handle/2005/2920

5. Calland, Noémie. L'EGCG et la delphinidine : deux nouvelles molécules naturelles inhibant l'entrée du virus de l'hépatite C : EGCG and delphinidin : two new natural inhibitors of hepatitis C virus entry.

Degree: Docteur es, Biochimie et biologie moléculaire, 2012, Université Lille II – Droit et Santé

URL: http://www.theses.fr/2012LIL2S031

► L’hépatite C est un problème majeur de santé publique qui touche environ 160 millions de personnes dans le monde. L’agent étiologique responsable de cette maladie,… (more)

▼ L’hépatite C est un problème majeur de santé publique qui touche environ 160 millions de personnes dans le monde. L’agent étiologique responsable de cette maladie, le virus de l’hépatite C (HCV), est un petit virus enveloppé dont le génome est codé par un acide ribonucléique (ARN) simple brin de polarité positive. Actuellement, il n’existe aucun vaccin contre ce pathogène et les traitements utilisés sont insatisfaisants du fait de leur spécificité d’action limitée. Ainsi, afin d’établir une thérapie antivirale efficace évitant l’apparition et la sélection de mutants de résistance aux antiviraux, l’utilisation de plusieurs agents antiviraux ciblant directement la particule virale (direct acting antiviral agents ou DAAs) en combinaison est préconisée. C’est pourquoi la découverte de nouveaux DAAs à large spectre d’action ciblant diverses étapes du cycle viral infectieux est indispensable.Au cours de ma thèse, nous avons identifié un nouvel inhibiteur de l’entrée du HCV : l’épigallocatéchine-3-gallate (EGCG). Cette molécule, extraite du thé vert, inhibe l’infection des cellules par le HCV. Plus précisément, en utilisant des particules rétrovirales pseudotypées avec les glycoprotéines d’enveloppe E1 et E2 du HCV, nous avons démontré que cette catéchine naturelle, agit à une étape très précoce de l’entrée virale, indépendamment du génotype. De même, en nous servant du virus produit en culture cellulaire, nous avons montré que cette molécule agit directement sur la particule virale. Puis, par RT-PCR quantitative (quantitative real-time polymerase chain reaction), nous avons confirmé l’inhibition de la liaison du virus à la surface cellulaire, en présence d’EGCG. Par conséquent, nos travaux suggèrent que l’EGCG interagit avec la particule virale, probablement en se liant aux glycoprotéines d’enveloppe virales, bloquant ainsi une étape initiale d’attachement entre le virus et les facteurs cellulaires présents à la surface de l’hépatocyte. Puis, en inhibant la transmission libre du virus, à l’aide, soit d’agarose, soit d’anticorps neutralisants, nous avons démontré que l’EGCG inhibe la transmission du virus de cellule à cellule. Enfin, nous avons montré que l’EGCG élimine le virus présent dans le surnageant de culture cellulaire après quatre passages successifs sur des cellules naïves.La concentration d’EGCG nécessaire pour inhiber la moitié de l’infection virale (IC50) en culture cellulaire est 11 µM. Ainsi, afin d’identifier de nouvelles molécules présentant un mode d’action similaire à celui de l’EGCG et possédant une meilleure activité antivirale, nous avons sélectionnés différentes molécules naturelles et les avons testés pour leur potentiel effet anti-HCV. C’est ainsi que le chlorure de delphinidine, une anthocyanidine, a également été identifié en tant que nouvelle molécule inhibitrice de l’entrée du HCV. De même que l’EGCG, le chlorure de delphinidine cible directement la particule virale à une étape précoce de l’entrée, indépendamment du génotype, probablement en inhibant l’attachement du virus à la surface… Advisors/Committee Members: Séron, Karin (thesis director).

Subjects/Keywords: EGCG; Delphinidine; Hépatite C; Hepatitis C virus

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Calland, N. (2012). L'EGCG et la delphinidine : deux nouvelles molécules naturelles inhibant l'entrée du virus de l'hépatite C : EGCG and delphinidin : two new natural inhibitors of hepatitis C virus entry. (Doctoral Dissertation). Université Lille II – Droit et Santé. Retrieved from http://www.theses.fr/2012LIL2S031

Chicago Manual of Style (16^th Edition):

Calland, Noémie. “L'EGCG et la delphinidine : deux nouvelles molécules naturelles inhibant l'entrée du virus de l'hépatite C : EGCG and delphinidin : two new natural inhibitors of hepatitis C virus entry.” 2012. Doctoral Dissertation, Université Lille II – Droit et Santé. Accessed January 17, 2021. http://www.theses.fr/2012LIL2S031.

MLA Handbook (7^th Edition):

Calland, Noémie. “L'EGCG et la delphinidine : deux nouvelles molécules naturelles inhibant l'entrée du virus de l'hépatite C : EGCG and delphinidin : two new natural inhibitors of hepatitis C virus entry.” 2012. Web. 17 Jan 2021.

Vancouver:

Calland N. L'EGCG et la delphinidine : deux nouvelles molécules naturelles inhibant l'entrée du virus de l'hépatite C : EGCG and delphinidin : two new natural inhibitors of hepatitis C virus entry. [Internet] [Doctoral dissertation]. Université Lille II – Droit et Santé 2012. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2012LIL2S031.

Council of Science Editors:

Calland N. L'EGCG et la delphinidine : deux nouvelles molécules naturelles inhibant l'entrée du virus de l'hépatite C : EGCG and delphinidin : two new natural inhibitors of hepatitis C virus entry. [Doctoral Dissertation]. Université Lille II – Droit et Santé 2012. Available from: http://www.theses.fr/2012LIL2S031

Addis Ababa University

6. BAYE, GELAW. THE PREVALENCE OF HBV, HCV AND MALARIA PARASITES IN BLOOD DONORS IN AMHARA AND TIGRAY NATIONAL STATES, ETHIOPIA .

Degree: 2008, Addis Ababa University

URL: http://etd.aau.edu.et/dspace/handle/123456789/2942

► Blood has long been recognized as a vehicle for transmission of infectious organisms, including viruses, bacteria, and parasites. The most important ones are HIV-1 and… (more)

▼ Blood has long been recognized as a vehicle for transmission of infectious organisms, including viruses, bacteria, and parasites. The most important ones are HIV-1 and 2, HBV, HCV, and malaria parasites. Determination of the prevalence of HBV, HCV and malaria parasites in a population in general, and blood donor in particular will certainly help in making health policy decisions. The primary aim of this study was to demonstrate the prevalence of HBV, HCV, and malaria parasites among healthy adult blood donors in Gondar, Bahirdar, Dessie and Mekele blood banks. Socio-demographic characteristics of the blood donors and the history of hepatitis virus infection, history of malaria infection together with the number of sexual partners in life and history of repeated donation was assessed by questionnaire. Of the blood donors 578 were males and 22 females. The age distribution ranges from 18 to 69 years and the maximum (59.5%) blood donation age category was between 19 to 28 years of age. Serum samples from 600 blood donors, 300 from Gondar and 100 each from the three study areas (Bahirdar, Dessie, and Mekele) were collected from December 2002 to February 2003. The over all prevalences of HBsAg, HCV and malaria parasites were 6.2%, 1.7% and 1% respectively. All hepatitis virus positive blood donors were males. The prevalence of HBsAg in age category 19 to 28 years was 62.2% (23/37) followed by age category 29 to 38 years (24.3%). Fifty percent (5/10) of HCV positive blood donors was in age category between 19 to 28 years. Single blood donors were more positive than the married ones (OR=1.9; 95%CI 0.8-4.6). In this study all positive blood donors for HBsAg and anti-HCV were not having the history of hepatitis virus infection and repeated blood donation was not found to be a risk factor for HBsAg and anti-HCV positivity (p=0.7 and p=0.8, respectively). Three hundred one blood donors were without sexual partners and 252 with only one sexual partner in life. Among the positives for HBsAg and HCV antibody, 59.5% and 20% respectively were with single sexual partner. The prevalence of HBsAg, and anti- HCV found by this study are quite important. Therefore, screening blood donors for both HBV and HCV infection is indispensable for safe blood transfusion. The limitations of the majority of serological tests in general, and the ACON test strip kit in particular are also considerable especially for anti-HCV determination during the window period. Asking blood donors for recent malaria infection and confirming negativity by viii laboratory tests need to be included in daily donor selection. Hepatitis B surface antigen detection may not rule out the over all prevalence of the disease. Therefore, determination of other markers including anti-HBS, anti- HBe, anti-HBC together with HCV antigen are being recommended in the future to assure safe blood donation. Advisors/Committee Members: Yohannes Mengistu (PhD) (advisor).

Subjects/Keywords: Hepatitis B virus; Hepatitis C virus; blood donor; malaria parasites; prevalence

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

BAYE, G. (2008). THE PREVALENCE OF HBV, HCV AND MALARIA PARASITES IN BLOOD DONORS IN AMHARA AND TIGRAY NATIONAL STATES, ETHIOPIA . (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/2942

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

BAYE, GELAW. “THE PREVALENCE OF HBV, HCV AND MALARIA PARASITES IN BLOOD DONORS IN AMHARA AND TIGRAY NATIONAL STATES, ETHIOPIA .” 2008. Thesis, Addis Ababa University. Accessed January 17, 2021. http://etd.aau.edu.et/dspace/handle/123456789/2942.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

BAYE, GELAW. “THE PREVALENCE OF HBV, HCV AND MALARIA PARASITES IN BLOOD DONORS IN AMHARA AND TIGRAY NATIONAL STATES, ETHIOPIA .” 2008. Web. 17 Jan 2021.

Vancouver:

BAYE G. THE PREVALENCE OF HBV, HCV AND MALARIA PARASITES IN BLOOD DONORS IN AMHARA AND TIGRAY NATIONAL STATES, ETHIOPIA . [Internet] [Thesis]. Addis Ababa University; 2008. [cited 2021 Jan 17]. Available from: http://etd.aau.edu.et/dspace/handle/123456789/2942.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

BAYE G. THE PREVALENCE OF HBV, HCV AND MALARIA PARASITES IN BLOOD DONORS IN AMHARA AND TIGRAY NATIONAL STATES, ETHIOPIA . [Thesis]. Addis Ababa University; 2008. Available from: http://etd.aau.edu.et/dspace/handle/123456789/2942

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Addis Ababa University

7. Jijiga, Edosa. Assessment of Transfusion Transmissible Infections Among Blood Donors (A six years study) and Strategy on Direct Laboratory Testing Cost of Blood Screening at National Blood Transfusion Service of Addis Ababa, Ethiopia.

Degree: 2014, Addis Ababa University

URL: http://etd.aau.edu.et/dspace/handle/123456789/5846

► Abstract Background: Hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and syphilis are the most serious infections transmitted during blood transfusion.… (more)

▼ Abstract Background: Hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and syphilis are the most serious infections transmitted during blood transfusion. In such a resource limited setting, cheaper and feasible alternative strategies for blood donations testing are speciﬁcally required. However, updated data on the transfusion transmissible infections (TTIs), and cost effective strategies of blood screening are lacking. Objective: To determine the prevalence of transfusion transmissible infections among blood donorsfrom July 2008 to July 2013and propose cost effective strategy of blood screening at National Blood Bank of Addis Ababa, Ethiopia. Methodology:A retrospective analysis of blood donors’ record covering the period from July 2008 to July 2013 was conducted. The data was collected from the National Blood Transfusion Services (NBTS) of Addis Ababa and includes category of all donors and result for TTI markers. In addition, direct laboratory costs of parallel versus sequential strategy of blood screening were compared. To compare the strategies we used the current price of the laboratory costs. Data was first exported to Excel spread sheet from the institution’s data base and then finally exported to SPSS version 16 software (SPSS INC, Chicago, IL, USA) for analysis.Data analysis was performed using scores and odds ratio using same software to look for an association between dependent and independent variables. P values less than 0.05 were considered significant. Result: A total of 173,207 consecutive blood donors were screened between 2008 and 2013.The overall seroprevalence rate ofHBV, HIV, HCV and syphilis of blood donors was 5.0%, 1.6%, 1.4% and 0.1%respectively. The HIV-HBV confection was higher among blood donors 135(41.79%) followed by HBV-HCV co-infection which accounts about 103(31.89%). Significantly increased seroprevalence of TTI’s was observed in the age groups of 17-25 and 2635 years. In this study, the difference in cost between the current in use strategy (Parallel) versus our proposed newly designed sequential testing algorithm was 746,773.90 ETB. Conclusion: A significant percentage of the blood donors harbor TTIs. Higher prevalence of TTIs was observed among youths and replacement donors. The direct laboratory cost analysis using current in use strategy (parallel) was higher than the newly designed sequential testing algorithm. Thus, the new strategy can be implemented to make screening of TTIs cost effective in the face of the current effort of large mobilization of voluntary blood donors in the country. Advisors/Committee Members: Aster Tsegaye(MSc, PhD) (advisor).

Subjects/Keywords: Hepatitis B virus (HBV); hepatitis C virus (HCV); (HIV); syphilis

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jijiga, E. (2014). Assessment of Transfusion Transmissible Infections Among Blood Donors (A six years study) and Strategy on Direct Laboratory Testing Cost of Blood Screening at National Blood Transfusion Service of Addis Ababa, Ethiopia. (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/5846

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jijiga, Edosa. “Assessment of Transfusion Transmissible Infections Among Blood Donors (A six years study) and Strategy on Direct Laboratory Testing Cost of Blood Screening at National Blood Transfusion Service of Addis Ababa, Ethiopia. ” 2014. Thesis, Addis Ababa University. Accessed January 17, 2021. http://etd.aau.edu.et/dspace/handle/123456789/5846.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jijiga, Edosa. “Assessment of Transfusion Transmissible Infections Among Blood Donors (A six years study) and Strategy on Direct Laboratory Testing Cost of Blood Screening at National Blood Transfusion Service of Addis Ababa, Ethiopia. ” 2014. Web. 17 Jan 2021.

Vancouver:

Jijiga E. Assessment of Transfusion Transmissible Infections Among Blood Donors (A six years study) and Strategy on Direct Laboratory Testing Cost of Blood Screening at National Blood Transfusion Service of Addis Ababa, Ethiopia. [Internet] [Thesis]. Addis Ababa University; 2014. [cited 2021 Jan 17]. Available from: http://etd.aau.edu.et/dspace/handle/123456789/5846.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jijiga E. Assessment of Transfusion Transmissible Infections Among Blood Donors (A six years study) and Strategy on Direct Laboratory Testing Cost of Blood Screening at National Blood Transfusion Service of Addis Ababa, Ethiopia. [Thesis]. Addis Ababa University; 2014. Available from: http://etd.aau.edu.et/dspace/handle/123456789/5846

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Addis Ababa University

8. Yacob, Mohammed. Prevalence of Hepatitis B, Hepatitis C and HIV among Chronic liver disease patients in selected hospitals, Addis Ababa, Ethiopia .

Degree: 2014, Addis Ababa University

URL: http://etd.aau.edu.et/dspace/handle/123456789/5853

► Abstract Introduction; Hepatitis B virus (HBV) and hepatitis C (HCV) virus is hepatotropic virus spread mainly through contaminated blood and blood products, sexual contact and… (more)

▼ Abstract Introduction; Hepatitis B virus (HBV) and hepatitis C (HCV) virus is hepatotropic virus spread mainly through contaminated blood and blood products, sexual contact and contaminated needles. Chronic infection by these viruses leads to slow progressive liver disease that over a period of up to 30 years may result in cirrhosis, chronic liver failure and hepatocellular carcinoma (HCC). HIV, HBV, and HCV infection share similar transmission routes and therefore co-infection is common. These viruses are prevalent in different parts of the world including Ethiopia there for this study shows the burden of these viruses in Ethiopia. Objective: To determine the prevalence of HBV, HCV and HIV infection among clinically diagnosed chronic liver disease patients visited at Black Lion, St. Paul and Armed force hospital Addis Ababa, Ethiopia. Method: Hospital based cross-sectional study was conducted in three selected hospitals of Addis Ababa over a period of 3 months (March2014- May 2014) on clinically diagnosed chronic liver disease patients. By using questionnaire brief history and risk factors was taken from each volunteering patient. Serum samples from each volunteering patients was screened for the presence of HBsAg and anti-HCV by ELISIA test kit and HIV by national test algorism. Result: A total of 117 participants who have chronic liver disease participated in the study, where 82 of them were males and the remaining 35 were females. The age distribution range form 18-78 years and the median age was 39 years. The overall prevalence of HBsAg, HCV and HIV was 34.2%, 18.8% and 9.4 respectively. The study participants had combined HBV/HIV, HCV/HIV and HBV/HCV infection which is possible because of their common modes of transmission. History of multiple sexual partner and blood transfusion also found statically significance with HBV and HCV virus infection respectively. Conclusion: The prevalence of HBV and HCV is high where as HIV is moderate among chronic liver disease patients and history of blood transfusion and multiple sexual partners was statistically associated with HCV and HBV infection respectively. Advisors/Committee Members: Ibrahim Ali, (BSc, MSC, PhD) (advisor).

Subjects/Keywords: Hepatitis B virus (HBV); hepatitis C (HCV); hepatotropic virus

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yacob, M. (2014). Prevalence of Hepatitis B, Hepatitis C and HIV among Chronic liver disease patients in selected hospitals, Addis Ababa, Ethiopia . (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/5853

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yacob, Mohammed. “Prevalence of Hepatitis B, Hepatitis C and HIV among Chronic liver disease patients in selected hospitals, Addis Ababa, Ethiopia .” 2014. Thesis, Addis Ababa University. Accessed January 17, 2021. http://etd.aau.edu.et/dspace/handle/123456789/5853.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yacob, Mohammed. “Prevalence of Hepatitis B, Hepatitis C and HIV among Chronic liver disease patients in selected hospitals, Addis Ababa, Ethiopia .” 2014. Web. 17 Jan 2021.

Vancouver:

Yacob M. Prevalence of Hepatitis B, Hepatitis C and HIV among Chronic liver disease patients in selected hospitals, Addis Ababa, Ethiopia . [Internet] [Thesis]. Addis Ababa University; 2014. [cited 2021 Jan 17]. Available from: http://etd.aau.edu.et/dspace/handle/123456789/5853.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yacob M. Prevalence of Hepatitis B, Hepatitis C and HIV among Chronic liver disease patients in selected hospitals, Addis Ababa, Ethiopia . [Thesis]. Addis Ababa University; 2014. Available from: http://etd.aau.edu.et/dspace/handle/123456789/5853

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Ryerson University

9. Zalai, Dora, Marta. Fatigue in chronic hepatitis C infection a mixed method study.

Degree: 2014, Ryerson University

URL: https://digital.library.ryerson.ca/islandora/object/RULA%3A2995

► Fatigue is a main patient reported outcome of chronic hepatitis C (HCV) infection; yet its contributors are unknown. Objectives: The study (1) evaluated fatigue predictors,… (more)

Subjects/Keywords: Hepatitis C.; Hepatitis C virus.; Fatigue; Sleep disorders

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zalai, Dora, M. (2014). Fatigue in chronic hepatitis C infection a mixed method study. (Thesis). Ryerson University. Retrieved from https://digital.library.ryerson.ca/islandora/object/RULA%3A2995

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zalai, Dora, Marta. “Fatigue in chronic hepatitis C infection a mixed method study.” 2014. Thesis, Ryerson University. Accessed January 17, 2021. https://digital.library.ryerson.ca/islandora/object/RULA%3A2995.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zalai, Dora, Marta. “Fatigue in chronic hepatitis C infection a mixed method study.” 2014. Web. 17 Jan 2021.

Vancouver:

Zalai, Dora M. Fatigue in chronic hepatitis C infection a mixed method study. [Internet] [Thesis]. Ryerson University; 2014. [cited 2021 Jan 17]. Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A2995.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zalai, Dora M. Fatigue in chronic hepatitis C infection a mixed method study. [Thesis]. Ryerson University; 2014. Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A2995

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Grandal Fustes, Marta. Caracterización epidemiológica y virológica en pacientes con infección crónica por el Virus de la Hepatitis C: impacto en el tratamiento con antivirales de acción directa .

Degree: 2019, Universidad da Coruña

URL: http://hdl.handle.net/2183/24358

► [Resumen] La infección por el Virus de la Hepatitis C (VHC) es un problema grave de salud pública mundial, que actualmente afecta a más de… (more)

▼ [Resumen] La infección por el Virus de la Hepatitis C (VHC) es un problema grave de salud pública mundial, que actualmente afecta a más de 71 millones de personas en todo el mundo, y que lidera una significativa morbilidad y mortalidad. Desde la aprobación de los nuevos antivirales de acción directa (AADs), el paradigma de la infección por VHC ha cambiado. Los regímenes con AADs son ahora el nuevo estándar de tratamiento frente al VHC con tasas de respuesta virológica sostenida (RVS) de más del 90%, de corta duración y sin apenas efectos adversos asociados. Sin embargo, en un primer momento, sus elevados costes supusieron una limitación para ofrecer un tratamiento global a los pacientes con infección por VHC. Esta situación fue resuelta en mayo de 2015 cuando el Sistema Nacional de Salud (SNS) español publicó el Plan Estratégico para el Abordaje de la Hepatitis C (PEAHC) que establecía los criterios para la priorización del tratamiento con los nuevos AADs. A pesar de las altas tasas de curación asociadas a los nuevos AADs superiores al 90%, existe todavía una proporción de pacientes entre un 2-10% que no alcanza una RVS. Entre las diferentes causas asociadas a esta falta de respuesta están numerosos factores como el grado de fibrosis hepática, la exposición previa a terapias con IFN, la carga viral, el genotipo viral o la presencia de mutaciones de resistencia (RASs) en regiones del genoma viral que son las dianas terapéuticas de los AADs (como NS5A). Además, las RASs generalmente se asocian a fracaso terapéutico cuando su presencia se combina con algunos de los demás factores relacionados con menores tasas de RVS. Todos estos factores han de tenerse en cuenta para optimizar la elección de tratamiento y su duración, con el fin de asegurar la mejor respuesta posible. En este contexto, los objetivos de este trabajo fueron, en primer lugar, caracterizar el perfil de la infección crónica por VHC en el área sanitaria de A Coruña, y evaluar el impacto del PEAHC en el abordaje del tratamiento de la infección en esta población. En segundo lugar, los objetivos fueron evaluar la prevalencia de RASs basales en NS5A en pacientes con genotipo 1a (G1a) y genotipo 3 (G3), y evaluar los beneficios de la realización de un estudio de resistencias para optimizar las estrategias terapéuticas disponibles. Los resultados obtenidos en el primer estudio, señalaron que el perfil de la infección crónica por VHC en el área sanitaria de A Coruña se caracterizaba por una prevalencia mayoritaria en varones (76,2%) con una media de edad de 50 ± 9,5 años, donde la cirrosis hepática (28,7%) y la co-infección por VIH (60,9%) fueron frecuentes. A nivel virológico, el virus presentó cargas virales elevadas y el genotipo mayoritario fue el 1 (66,1%), subtipo 1a (41,5%), seguido del G3 (16,8%). Durante el año 2015 el 52,7% de los pacientes iniciaron tratamiento con una tasa de RVS global superior al 96%. No se observaron diferencias significativas entre esta RVS y factores relacionados con peor respuesta al tratamiento… Advisors/Committee Members: Poveda, Eva (advisor), Pedreira Andrade, José Domingo (advisor).

Subjects/Keywords: Virus de la hepatitis C; Hepatitis C-Tratamiento; Antivirales-Investigación

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Grandal Fustes, M. (2019). Caracterización epidemiológica y virológica en pacientes con infección crónica por el Virus de la Hepatitis C: impacto en el tratamiento con antivirales de acción directa . (Doctoral Dissertation). Universidad da Coruña. Retrieved from http://hdl.handle.net/2183/24358

Chicago Manual of Style (16^th Edition):

Grandal Fustes, Marta. “Caracterización epidemiológica y virológica en pacientes con infección crónica por el Virus de la Hepatitis C: impacto en el tratamiento con antivirales de acción directa .” 2019. Doctoral Dissertation, Universidad da Coruña. Accessed January 17, 2021. http://hdl.handle.net/2183/24358.

MLA Handbook (7^th Edition):

Grandal Fustes, Marta. “Caracterización epidemiológica y virológica en pacientes con infección crónica por el Virus de la Hepatitis C: impacto en el tratamiento con antivirales de acción directa .” 2019. Web. 17 Jan 2021.

Vancouver:

Grandal Fustes M. Caracterización epidemiológica y virológica en pacientes con infección crónica por el Virus de la Hepatitis C: impacto en el tratamiento con antivirales de acción directa . [Internet] [Doctoral dissertation]. Universidad da Coruña; 2019. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2183/24358.

Council of Science Editors:

Grandal Fustes M. Caracterización epidemiológica y virológica en pacientes con infección crónica por el Virus de la Hepatitis C: impacto en el tratamiento con antivirales de acción directa . [Doctoral Dissertation]. Universidad da Coruña; 2019. Available from: http://hdl.handle.net/2183/24358

11. Margusino Framiñán, Luis. Efectividad y seguridad de los antivirales de acción directa frente al virus de la hepatitis C: foco en subpoblaciones especiales .

Degree: 2020, Universidad da Coruña

URL: http://hdl.handle.net/2183/26574

► [Resumen] El virus de la hepatitis C (VHC) es un virus ácido ribonucleico (ARN) monocatenario identificado como el agente etiológico de la hepatitis C. El… (more)

▼ [Resumen] El virus de la hepatitis C (VHC) es un virus ácido ribonucleico (ARN) monocatenario identificado como el agente etiológico de la hepatitis C. El principal órgano diana del VHC es el hígado, donde puede desarrollar una hepatitis aguda y/o crónica que, a largo plazo, puede causar fibrosis hepática, cirrosis hepática, carcinoma hepatocelular (CHC) y, finalmente, la muerte. Se han aislado 6 genotipos principales del VHC, con desigual distribución a nivel mundial y un séptimo genotipo en algunos individuos. Esta heterogeneidad genética tiene importantes implicaciones a nivel de la evolución de la enfermedad hepática del paciente infectado y en la selección y efectividad del tratamiento antiviral en práctica clínica. Particularmente, la infección crónica por el genotipo 3 del VHC tiene una progresión más rápida en todos los estadios de la enfermedad hepática y peor respuesta a los tratamientos antivirales disponibles. El objetivo del tratamiento antiviral frente al VHC es curar la infección por este virus para prevenir las complicaciones hepáticas y enfermedades extrahepáticas relacionadas (necroinflamación hepática, fibrosis, cirrosis, descompensación de cirrosis, CHC, manifestaciones graves extrahepáticas y muerte), mejorar la calidad de vida, eliminar el estigma y evitar la transmisión posterior del VHC. Según las sociedades científicas de referencia en nuestro ámbito, todos los pacientes con una hepatitis C crónica (HCC), monoinfectados o coinfectados con el virus de la inmunodeficiencia humana adquirida (VIH), naïve o previamente tratados con fallo terapéutico, y sin contraindicaciones para el tratamiento, deben ser considerados candidatos a tratamiento antiviral, independientemente de su grado de fibrosis. El tratamiento de la infección crónica por VHC ha experimentado una evolución muy importante, especialmente en las últimas dos décadas, conforme se han autorizado nuevos medicamentos más eficaces y seguros frente a este virus. Los resultados de los ensayos clínicos han posicionado muy recientemente a los antivirales de acción directa (AAD) como los medicamentos de elección en el tratamiento de la infección crónica por VHC. Existen tres amplias clases de antivirales de acción directa que actúan a distintos niveles del ciclo biológico del VHC: inhibidores de proteasa NS3/4A, inhibidores del complejo de replicación NS5A e inhibidores de la polimerasa NS5B, que se dividen en inhibidores de nucleos(t)idos o inhibidores no nucleósidos. La selección del tratamiento antiviral es independiente de la coinfección por VIH y depende básicamente de tres variables: genotipo/subtipo de VHC, gravedad de enfermedad hepática y/o tratamientos previos. Otras variables dependientes del virus, del paciente o del tratamiento basal de paciente podrían condicionar el resultado del tratamiento antiviral frente al virus de la hepatitis C en la práctica clínica. Por lo tanto, es importante conocer la efectividad y seguridad en práctica clínica real de los antivirales de acción directa en pacientes diagnosticados de hepatitis C… Advisors/Committee Members: Castro-Iglesias, Ángeles (advisor).

Subjects/Keywords: Antivirales-Investigación; Hepatitis C-Tratamiento; Virus de la hepatitis C

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Margusino Framiñán, L. (2020). Efectividad y seguridad de los antivirales de acción directa frente al virus de la hepatitis C: foco en subpoblaciones especiales . (Doctoral Dissertation). Universidad da Coruña. Retrieved from http://hdl.handle.net/2183/26574

Chicago Manual of Style (16^th Edition):

Margusino Framiñán, Luis. “Efectividad y seguridad de los antivirales de acción directa frente al virus de la hepatitis C: foco en subpoblaciones especiales .” 2020. Doctoral Dissertation, Universidad da Coruña. Accessed January 17, 2021. http://hdl.handle.net/2183/26574.

MLA Handbook (7^th Edition):

Margusino Framiñán, Luis. “Efectividad y seguridad de los antivirales de acción directa frente al virus de la hepatitis C: foco en subpoblaciones especiales .” 2020. Web. 17 Jan 2021.

Vancouver:

Margusino Framiñán L. Efectividad y seguridad de los antivirales de acción directa frente al virus de la hepatitis C: foco en subpoblaciones especiales . [Internet] [Doctoral dissertation]. Universidad da Coruña; 2020. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2183/26574.

Council of Science Editors:

Margusino Framiñán L. Efectividad y seguridad de los antivirales de acción directa frente al virus de la hepatitis C: foco en subpoblaciones especiales . [Doctoral Dissertation]. Universidad da Coruña; 2020. Available from: http://hdl.handle.net/2183/26574

12. Villegas Chiroque, Miguel. Factores predictivos de respuesta al tratamiento contra la hepatitis C crónica en pacientes atendidos en el Hospital Militar Central Lima Perú, 2006-2011.

Degree: 2013, National University of San Marcos

URL: http://hdl.handle.net/20.500.12672/3409

► – We performed a retrospective study of cases and controls to assess predictors of efficacy of combination therapy with pegylated interferon alpha (Peg IFN-) and… (more)

Subjects/Keywords: Hepatitis C - Tratamiento; Virus de la hepatitis C

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Villegas Chiroque, M. (2013). Factores predictivos de respuesta al tratamiento contra la hepatitis C crónica en pacientes atendidos en el Hospital Militar Central Lima Perú, 2006-2011. (Thesis). National University of San Marcos. Retrieved from http://hdl.handle.net/20.500.12672/3409

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Villegas Chiroque, Miguel. “Factores predictivos de respuesta al tratamiento contra la hepatitis C crónica en pacientes atendidos en el Hospital Militar Central Lima Perú, 2006-2011.” 2013. Thesis, National University of San Marcos. Accessed January 17, 2021. http://hdl.handle.net/20.500.12672/3409.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Villegas Chiroque, Miguel. “Factores predictivos de respuesta al tratamiento contra la hepatitis C crónica en pacientes atendidos en el Hospital Militar Central Lima Perú, 2006-2011.” 2013. Web. 17 Jan 2021.

Vancouver:

Villegas Chiroque M. Factores predictivos de respuesta al tratamiento contra la hepatitis C crónica en pacientes atendidos en el Hospital Militar Central Lima Perú, 2006-2011. [Internet] [Thesis]. National University of San Marcos; 2013. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/20.500.12672/3409.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Villegas Chiroque M. Factores predictivos de respuesta al tratamiento contra la hepatitis C crónica en pacientes atendidos en el Hospital Militar Central Lima Perú, 2006-2011. [Thesis]. National University of San Marcos; 2013. Available from: http://hdl.handle.net/20.500.12672/3409

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Ottawa

13. Nasheri Ardekan, Neda. Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus .

Degree: 2015, University of Ottawa

URL: http://hdl.handle.net/10393/32480

► Hepatitis C virus (HCV) is a growing health concern in Canada and around the world, as it currently infects 3% of the global population. While… (more)

▼ Hepatitis C virus (HCV) is a growing health concern in Canada and around the world, as it currently infects 3% of the global population. While there is no vaccine available against this virus, novel and effective treatment regimens have improved prospects for the cure of HCV. Complications caused by HCV can lead to severe liver disease and even death. The limited viral proteome forces HCV to rely heavily on various host factors for its replication. Additionally HCV modulates the host physiology to facilitate its pathogenesis; consequently, the in dept study of essential host-virus interactions expands our understandingof how the virus and related species commandere host cell machinery. This understanding can help create new therapeutic strategies, which may have applications towards HCV and other related RNA viruses. While numerous studies have demonstrated that HCV modulates the abundance of various host proteins, the systematic study of the virus’s effect on the enzymatic activity has been relatively unexplored. For this reason, activity-based protein profiling (ABPP) was applied to study the changes in the activity of host enzymes during HCV replication. ABPP is a functional proteomics technique that employs active site-directed probe (ABP) to report on the activity of enzymes within complex proteomes, such as living cells. Herein, directed and non-directed ABPs were employed for specific as well as global profiling of the alterations in the activity of cellular enzymes during HCV replication. As a result, essential host enzymes that are differentially active during HCV infection were identified. Furthermore, I have developed a quantitative ABPP method for relative quantification of the cellular enzymes activity during HCV infection. These results contribute to the discovery of disease-associated biomarkers, with diagnostic significance, and aid in the identification of potential targets for therapeutic interventions. In addition to developing protein-based tools to study host-virus interactions, I employed a novel technique to investigate the interactions of micro-RNA 122 (miR-122), an essential HCV host factor, with the viral RNA genome. This in vitro screening approach, interrogates the folding of HCV RNA using viral RNA-coated magnetic bead (VRB) to determine target site accessibility for RNA silencing. This method predicts the relative affinity of small RNAs towards HCV genomic RNA that are not easily predicted by informatic means, and led to discovery of potent miR-122 interaction site within the large, highly-structured HCV RNA genome. For that reason, VRB assay may represent an attractive tool for the examination of target site accessibility for RNA silencing.

Subjects/Keywords: Hepatitis C Virus; Activity-Based Protein Profiling

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nasheri Ardekan, N. (2015). Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/32480

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nasheri Ardekan, Neda. “Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus .” 2015. Thesis, University of Ottawa. Accessed January 17, 2021. http://hdl.handle.net/10393/32480.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nasheri Ardekan, Neda. “Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus .” 2015. Web. 17 Jan 2021.

Vancouver:

Nasheri Ardekan N. Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus . [Internet] [Thesis]. University of Ottawa; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10393/32480.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nasheri Ardekan N. Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus . [Thesis]. University of Ottawa; 2015. Available from: http://hdl.handle.net/10393/32480

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Ottawa

14. Burke, Stephanie. Generalized Impairment of CD8+ T-cells in HCV Mono- and HIV-HCV Co-infection .

Degree: 2015, University of Ottawa

URL: http://hdl.handle.net/10393/32770

► Chronic hepatitis C virus (HCV) infection has global effects on the immune system. CD8+ T-cells, responsible for viral clearance and control, are dysfunctional for as… (more)

Subjects/Keywords: Hepatitis C Virus; CD8+ T cell; HIV

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Burke, S. (2015). Generalized Impairment of CD8+ T-cells in HCV Mono- and HIV-HCV Co-infection . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/32770

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Burke, Stephanie. “Generalized Impairment of CD8+ T-cells in HCV Mono- and HIV-HCV Co-infection .” 2015. Thesis, University of Ottawa. Accessed January 17, 2021. http://hdl.handle.net/10393/32770.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Burke, Stephanie. “Generalized Impairment of CD8+ T-cells in HCV Mono- and HIV-HCV Co-infection .” 2015. Web. 17 Jan 2021.

Vancouver:

Burke S. Generalized Impairment of CD8+ T-cells in HCV Mono- and HIV-HCV Co-infection . [Internet] [Thesis]. University of Ottawa; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10393/32770.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Burke S. Generalized Impairment of CD8+ T-cells in HCV Mono- and HIV-HCV Co-infection . [Thesis]. University of Ottawa; 2015. Available from: http://hdl.handle.net/10393/32770

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

15. Marsh, Katherine A. Characterization of the Hepatitis C Virus Life Cycle and Regulation of the Capsid Protein.

Degree: 2012, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/9320

► With more than 170 million people infected, hepatitis C virus (HCV) is a global health burden causing cirrhosis, liver steatosis, and hepatocellular carcinoma. As no… (more)

▼ With more than 170 million people infected, hepatitis C virus (HCV) is a global health burden causing cirrhosis, liver steatosis, and hepatocellular carcinoma. As no prophylactic vaccine is available and the current treatments are only efficacious in a subset of patients, the identification of novel drug targets and development of better therapies are urgently needed. Because an infectious cell culture system was not developed until 2005, HCV research previously focused on particular isolated aspects of the viral life cycle such as RNA replication and entry recapitulated by replicons and HCV pseudoparticles, respectively. Hence, we utilized the relatively new infectious cell culture system to perform studies characterizing the kinetics of the entire life cycle. Specifically, we have defined the dynamics of HCV RNA amplification, HCV protein accumulation, and release of infectious virions. Although all ten viral proteins are translated as one polyprotein which is then processed into individual proteins, our data indicates that the core protein, which binds and encapsidates the viral genome, is differentially regulated throughout infection relative to the other viral proteins NS3 and NS5B. While NS3 accumulates gradually over time and parallels the amplification HCV RNA, core accumulation remains undetectable prior to HCV RNA replication and then rapidly increase later in the life cycle. Investigation of the molecular mechanism effecting differential core accumulation revealed that core is unstable early in the life cycle before RNA amplification, but becomes stable late in the life cycle after RNA replication. Functional RNAi knockdown studies indicated that the cellular factors E6AP and PA28γ are involved in degrading core early in the life cycle. Additionally, we show in transient transfection experiments that HCV RNA is sufficient to induce the intracellular accumulation and stabilization of core. As such we speculate HCV has evolved a strategy for ensuring that when HCV RNA levels are low that it is first used to generate viral proteins and replicate the viral genome to adequate levels before excess viral RNA triggers core stabilization and subsequent assembly. Hence, this study characterizes the kinetics of the HCV life cycle and identifies a novel regulation of core. Advisors/Committee Members: Uprichard, Susan L. (advisor), McLachlan, Alan (committee member), Lipton, Howard (committee member), He, Bin (committee member), Tyner, Angela (committee member).

Subjects/Keywords: hepatitis C virus; viral life cycle; capsid

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Marsh, K. A. (2012). Characterization of the Hepatitis C Virus Life Cycle and Regulation of the Capsid Protein. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/9320

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Marsh, Katherine A. “Characterization of the Hepatitis C Virus Life Cycle and Regulation of the Capsid Protein.” 2012. Thesis, University of Illinois – Chicago. Accessed January 17, 2021. http://hdl.handle.net/10027/9320.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Marsh, Katherine A. “Characterization of the Hepatitis C Virus Life Cycle and Regulation of the Capsid Protein.” 2012. Web. 17 Jan 2021.

Vancouver:

Marsh KA. Characterization of the Hepatitis C Virus Life Cycle and Regulation of the Capsid Protein. [Internet] [Thesis]. University of Illinois – Chicago; 2012. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10027/9320.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Marsh KA. Characterization of the Hepatitis C Virus Life Cycle and Regulation of the Capsid Protein. [Thesis]. University of Illinois – Chicago; 2012. Available from: http://hdl.handle.net/10027/9320

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queen Mary, University of London

16. Javaid, Alia. Development of novel model systems to assess replication of patient derived hepatitis C virus in tissue culture.

Degree: PhD, 2015, Queen Mary, University of London

URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12872 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775152

► 1. Introduction: The development of novel therapies for chronic hepatitis C virus (HCV) infection could potentially be streamlined by using patient-derived model systems in which… (more)

▼ 1. Introduction: The development of novel therapies for chronic hepatitis C virus (HCV) infection could potentially be streamlined by using patient-derived model systems in which drugs can be tested on patient derived viral strains prior to embarking upon clinical trials. Such models have been hampered by difficulties in maintaining primary human hepatocytes (PHHs) from infected individuals in culture and by the lack of a replication model system for patient derived virus. Most in vitro models to date do not comprise individual patient virus from all strains of HCV and hence novel antivirals cannot be tested on them. The aim of this research was to develop novel models of replication of HCV that will allow new drugs to be tested against all viral genotypes. We have examined two models - an ex vivo liver biopsy model and an HCV monocyte-hepatocyte fusion model. 2. Methods: Liver biopsy fragments from patients with chronic HCV infection were studied to determine whether or not they could be used as a replication model. Biopsy fragments were incubated with DMEM alone or with antiviral drugs for 24h and 48h and viral replication assayed by RT-PCR for HCV RNA. Similar experiments were done with isolated primary human hepatocytes (PHHs) from patients with chronic HCV infection which were then compared with liver biopsy fragments. Various methods were used to extend the longevity of 6 PHHs. In later experiments we examined a novel model in which CD14 positive monocytes derived from patients with active HCV infection were fused with different liver cell lines in order to observe HCV replication. In this later model viral replication was observed and drug validation experiments were performed examining the effect of telaprevir on infected hepatocytes from genotype 1 and genotype 3 patients. 3. Results: Viral replication was observed in both models. The mean viral RNA concentration in biopsies from patients with genotype 1 HCV was significantly lower after 24 hours' incubation with telaprevir compared to unsupplemented medium (P=0.0015). Telaprevir did not have an effect on HCV RNA levels in biopsies from patients with genotypes 2 or 3 HCV. Viability of PHHs was reduced compared to intact biopsy fragments. In the HCV-replication fusion model, HCV expression was higher in fused cells compared to unfused monocytes (p=0.0007). Optimal fusion conditions were achieved by using monocytes and Huh 7.5s in a 1:1 ratio and using 3 minutes incubation in PEG with pH of 7. HCV expression was highest during the first 7 days in fused cells and there was a significant decline in HCV RNA during subsequent days (p=0.002). Viral protein production was observed in fused cells by indirect immunofluorescence, which confirmed viral replication. HCV was successfully transferred to Huh7.5 cells using the monocyte 'capture-fusion' approach. Telaprevir showed greater antiviral efficacy in fused/infected cells with genotype 1 compared to those with genotype 3 strain of HCV. Interferon's activity was compromised by transfecting Huh 7.5 7 cells with PIV5…

Subjects/Keywords: Medicine; hepatitis C virus; novel therapies

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Javaid, A. (2015). Development of novel model systems to assess replication of patient derived hepatitis C virus in tissue culture. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/12872 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775152

Chicago Manual of Style (16^th Edition):

Javaid, Alia. “Development of novel model systems to assess replication of patient derived hepatitis C virus in tissue culture.” 2015. Doctoral Dissertation, Queen Mary, University of London. Accessed January 17, 2021. http://qmro.qmul.ac.uk/xmlui/handle/123456789/12872 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775152.

MLA Handbook (7^th Edition):

Javaid, Alia. “Development of novel model systems to assess replication of patient derived hepatitis C virus in tissue culture.” 2015. Web. 17 Jan 2021.

Vancouver:

Javaid A. Development of novel model systems to assess replication of patient derived hepatitis C virus in tissue culture. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2015. [cited 2021 Jan 17]. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12872 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775152.

Council of Science Editors:

Javaid A. Development of novel model systems to assess replication of patient derived hepatitis C virus in tissue culture. [Doctoral Dissertation]. Queen Mary, University of London; 2015. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12872 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775152

University of New South Wales

17. Bebek, Filip. Towards the identification of novel Interferon-Alpha induced anti-Hepatitis C Virus effectors.

Degree: Biotechnology & Biomolecular Sciences, 2012, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/52281 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10953/SOURCE01?view=true

► Hepatitis C virus (HCV) infection is primarily treated with regimens that contain pegylated interferon alpha (PEG-IFN-alpha). IFN induces antiviral effects through the up-regulation of many… (more)

▼ Hepatitis C virus (HCV) infection is primarily treated with regimens that contain pegylated interferon alpha (PEG-IFN-alpha). IFN induces antiviral effects through the up-regulation of many interferon-stimulated genes (ISGs). While many ISGs have previously been identified, limitations of screening approaches employed to date raise the possibility that other anti-HCV ISGs are yet to be discovered. In the present study, a novel screening strategy combined suppression subtractive hybridisation (SSH) and recombinant Dicer generated siRNA pools to screen for anti-HCV ISGs - utilising a replicon model of HCV which is sensitive to IFN-alpha, and in which the impact on HCV replication can be readily assessed through the incorporation of a bicistronic luciferase reporter gene. This approach does not require a priori gene sequence data, and thereby opens up the possibility of detecting the anti-HCV activity of novel genes, functional polymorphisms and splice variants. SSH and its related technique mirror orientation selection (MOS) were employed to isolate differentially expressed genes from IFN-alpha treated Huh-7 cells. The isolated SSH and MOS genes were cross-referenced with microarray data to identify likely mediators of the anti-HCV replicon effects of IFN-alpha treatment. Subsequently, SSH/MOS cDNA clones were used to produce complementary dsRNA, which was digested with recombinant Dicer to generate target-specific siRNA pools, that were then screened for their ability to suppress the effects of IFN (using luciferase activity as a measure of replicon RNA copy number) following transfection into the stable HCV-replicon cell line (Huh-7 Luc). The list of positive screen hits included ZC3HAV1 and IFIT1. Further validation experiments showed the long isoform of ZC3HAV1 to be a new bona fide anti-replicon ISG. Thus, this study demonstrates the utility of unbiased screening approaches in better understanding how IFN-alpha limits HCV replication. Advisors/Committee Members: Rivory, Laurent, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, White, Peter, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW.

Subjects/Keywords: ZC3HAV1; Hepatitis C Virus; Interferon stimulated genes

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bebek, F. (2012). Towards the identification of novel Interferon-Alpha induced anti-Hepatitis C Virus effectors. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/52281 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10953/SOURCE01?view=true

Chicago Manual of Style (16^th Edition):

Bebek, Filip. “Towards the identification of novel Interferon-Alpha induced anti-Hepatitis C Virus effectors.” 2012. Doctoral Dissertation, University of New South Wales. Accessed January 17, 2021. http://handle.unsw.edu.au/1959.4/52281 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10953/SOURCE01?view=true.

MLA Handbook (7^th Edition):

Bebek, Filip. “Towards the identification of novel Interferon-Alpha induced anti-Hepatitis C Virus effectors.” 2012. Web. 17 Jan 2021.

Vancouver:

Bebek F. Towards the identification of novel Interferon-Alpha induced anti-Hepatitis C Virus effectors. [Internet] [Doctoral dissertation]. University of New South Wales; 2012. [cited 2021 Jan 17]. Available from: http://handle.unsw.edu.au/1959.4/52281 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10953/SOURCE01?view=true.

Council of Science Editors:

Bebek F. Towards the identification of novel Interferon-Alpha induced anti-Hepatitis C Virus effectors. [Doctoral Dissertation]. University of New South Wales; 2012. Available from: http://handle.unsw.edu.au/1959.4/52281 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10953/SOURCE01?view=true

University of New South Wales

18. Walker, Melanie. Characterising viral evolution and the host humoral immune response in early primary HCV infection.

Degree: Medical Sciences, 2018, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/59598 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:49083/SOURCE02?view=true

► Transmission of hepatitis C virus (HCV) is associated with a strong genetic bottleneck with 1-3 transmitted/founder (T/F) viruses establishing infection followed by a second genetic… (more)

▼ Transmission of hepatitis C virus (HCV) is associated with a strong genetic bottleneck with 1-3 transmitted/founder (T/F) viruses establishing infection followed by a second genetic bottleneck at ~100 days post-infection if chronicity is established. The first bottleneck is hypothesised to be driven by efficiency of cell entry, as observed in HIV. Examination of the second bottleneck has revealed T/F viruses are replaced by new variants that carry mutations within the Envelope region, suggesting that antibody responses are driving immune escape in early infection. The aim of this study was to compare, in a rare cohort of very recently HCV-infected individuals, the viral and host immune characteristics between clearers and chronic progressors. The timing and potency of the developing HCV specific antibody responses were examined between the two groups and contrasted against how the viral population was evolving phenotypically, in terms of in vitro infectivity and CD81 binding, over the course of infection.The sequence analysis of the viral quasispecies over the course of infection suggested that the developing humoral immune response targeted epitopes that overlapped with CD81 binding sites. Using HCV pseudo-particle (HCVpp) generated with autologous Envelopes, it was determined that efficient cell entry was a phenotypic trait of variants circulating early in infection, and was associated with higher binding to the host receptor, CD81.HCVpp neutralisation assays showed that early and potent neutralising antibody (nAb) responses occurred in clearer subjects prior to extinction of the T/F virus and were associated with no emergence of new viral variants, whereas in chronic progressors nAbs emerged after loss of T/F variants and after new ‘chronic variants’ had emerged. The early nAb response in clearers was associated with IgA as well as IgG1 and IgG3 responses.Finally, it was observed that when an anti-E2 IgG1 response was present, both CD81 binding and infectivity decreased. However, in the absence of humoral immune response, an increase in entry efficiency via CD81 occurred.The findings indicate that entry competent variants dominate the early phase of infection and that early nAb activity associated with both IgG3 and IgG1 subclasses appear to be essential to prevent emergence of new HCV variants and development of chronic infection. Results presented in this thesis advance our understanding of the interplay between host and viral responses, which is critical to inform vaccine design.

Subjects/Keywords: Viral evolution; Hepatitis C Virus; Humoral immunity

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Walker, M. (2018). Characterising viral evolution and the host humoral immune response in early primary HCV infection. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/59598 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:49083/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Walker, Melanie. “Characterising viral evolution and the host humoral immune response in early primary HCV infection.” 2018. Doctoral Dissertation, University of New South Wales. Accessed January 17, 2021. http://handle.unsw.edu.au/1959.4/59598 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:49083/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Walker, Melanie. “Characterising viral evolution and the host humoral immune response in early primary HCV infection.” 2018. Web. 17 Jan 2021.

Vancouver:

Walker M. Characterising viral evolution and the host humoral immune response in early primary HCV infection. [Internet] [Doctoral dissertation]. University of New South Wales; 2018. [cited 2021 Jan 17]. Available from: http://handle.unsw.edu.au/1959.4/59598 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:49083/SOURCE02?view=true.

Council of Science Editors:

Walker M. Characterising viral evolution and the host humoral immune response in early primary HCV infection. [Doctoral Dissertation]. University of New South Wales; 2018. Available from: http://handle.unsw.edu.au/1959.4/59598 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:49083/SOURCE02?view=true

19. Potel, Julie. Caractérisation d'inhibiteurs de l'entrée du Virus de l'Hépatite C : Characterisation of HCV entry inhibitors.

Degree: Docteur es, Bactériologie - virologie, 2012, Université Lille II – Droit et Santé

URL: http://www.theses.fr/2012LIL2S037

►

L’infection par le Virus de l’Hépatite C (VHC) est un problème majeur de santépublique touchant environ 170 millions de personnes dans le monde. A l’heure… (more)

▼

L’infection par le Virus de l’Hépatite C (VHC) est un problème majeur de santépublique touchant environ 170 millions de personnes dans le monde. A l’heure actuelle, il n’existe aucun vaccin pour lutter contre le VHC et les traitements curatifs disponibles sont chers, donnent lieu à des effets secondaires très sévères et ne sont efficaces que pour une partie des patients. Le développement de nouvelles stratégies antivirales représente donc un enjeu crucial dans la lutte contre le VHC. Dans le but de développer de nouvelles molécules bloquant différentes étapes du cycle viral, une meilleure compréhension de chacune des ces étapes est nécessaire. Au cours de mon travail de thèse, nous avons étudier le mécanisme d’entrée du VHC dans ses cellules cibles, les hépatocytes. Dans un premier temps nous avons caractérisé un inhibiteur naturel de l’entrée du VHC, appelé EWI-2wint. Ce travail a notamment permis de mettre en évidence l’importance de la dynamique membranaire de l’un des récepteurs du virus, la protéine CD81, dans ce processus. Dans un second axe, nous avons étudié l’effet de la monensine sur l’infection par le VHC. Nous avons ainsi montré que cet inhibiteur pharmacologique bloque une étape tardive du processus d’entrée du VHC.L’ensemble des données accumulées au cours de ma thèse permettent de mieux comprendre le mécanisme d’entrée du VHC et ouvrent la voie au développement de nouveaux outils thérapeutiques.

Hepatitis C, whose causal agent is called Hepatitis C Virus (HCV), is a global health burden with about 170 million people infected. Currently, no vaccine exists again HCV and treatments are effective for only a part of infected people. Therefore, new treatments are urgently needed, as well as a better understanding of the viral life cycle.To do so, we studied the entry process of HCV in its targets cells through the characterisation of HCV entry inhibitors. Firstly, we have shown that EWI-2wint, a natural inhibitor of HCV entry, blocks this process by changing the partitionning of CD81, one of the HCV receptors. In addition, we have studied the effect of monensin on HCV infection and found that this pharmacological inhibitor impairs a late step of HCV entry.Altogether, our results allow a better understading of the HCV entry process and open the way to the development of new therapeutic agents.

Advisors/Committee Members: Cocquerel, Laurence (thesis director).

Subjects/Keywords: EWI-2wint; Virus de l’Hépatite C; Hepatitis C Virus

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Potel, J. (2012). Caractérisation d'inhibiteurs de l'entrée du Virus de l'Hépatite C : Characterisation of HCV entry inhibitors. (Doctoral Dissertation). Université Lille II – Droit et Santé. Retrieved from http://www.theses.fr/2012LIL2S037

Chicago Manual of Style (16^th Edition):

Potel, Julie. “Caractérisation d'inhibiteurs de l'entrée du Virus de l'Hépatite C : Characterisation of HCV entry inhibitors.” 2012. Doctoral Dissertation, Université Lille II – Droit et Santé. Accessed January 17, 2021. http://www.theses.fr/2012LIL2S037.

MLA Handbook (7^th Edition):

Potel, Julie. “Caractérisation d'inhibiteurs de l'entrée du Virus de l'Hépatite C : Characterisation of HCV entry inhibitors.” 2012. Web. 17 Jan 2021.

Vancouver:

Potel J. Caractérisation d'inhibiteurs de l'entrée du Virus de l'Hépatite C : Characterisation of HCV entry inhibitors. [Internet] [Doctoral dissertation]. Université Lille II – Droit et Santé 2012. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2012LIL2S037.

Council of Science Editors:

Potel J. Caractérisation d'inhibiteurs de l'entrée du Virus de l'Hépatite C : Characterisation of HCV entry inhibitors. [Doctoral Dissertation]. Université Lille II – Droit et Santé 2012. Available from: http://www.theses.fr/2012LIL2S037

Universitat de Barcelona

20. Fernández Carrillo, Carlos. Nuevos factores del hospedador en la fisiopatología y la respuesta al tratamiento antiviral de la infección por el virus de la hepatitis C.

Degree: 2017, Universitat de Barcelona

URL: http://hdl.handle.net/10803/586384

► Using Translational Medicine, in this work we studied 2 key host elements in HCV infection: P-bodies and IFNL4/IFNL3 SNPs. CONCLUSIONS: 1. HCV infection impairs P-bodies… (more)

Subjects/Keywords: Virus de l'hepatitis C; Virus de la hepatitis C; Hepatitis C virus; Interferó; Interferón; Interferon; Ciències de la Salut; 616.9

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fernández Carrillo, C. (2017). Nuevos factores del hospedador en la fisiopatología y la respuesta al tratamiento antiviral de la infección por el virus de la hepatitis C. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/586384

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fernández Carrillo, Carlos. “Nuevos factores del hospedador en la fisiopatología y la respuesta al tratamiento antiviral de la infección por el virus de la hepatitis C.” 2017. Thesis, Universitat de Barcelona. Accessed January 17, 2021. http://hdl.handle.net/10803/586384.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fernández Carrillo, Carlos. “Nuevos factores del hospedador en la fisiopatología y la respuesta al tratamiento antiviral de la infección por el virus de la hepatitis C.” 2017. Web. 17 Jan 2021.

Vancouver:

Fernández Carrillo C. Nuevos factores del hospedador en la fisiopatología y la respuesta al tratamiento antiviral de la infección por el virus de la hepatitis C. [Internet] [Thesis]. Universitat de Barcelona; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10803/586384.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fernández Carrillo C. Nuevos factores del hospedador en la fisiopatología y la respuesta al tratamiento antiviral de la infección por el virus de la hepatitis C. [Thesis]. Universitat de Barcelona; 2017. Available from: http://hdl.handle.net/10803/586384

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New Mexico

21. Shea, Tanner K. CAN A SEX BIAS BE A GOOD THING: MODELING SPONTANEOUS CLEARANCE AND SEXUAL SUSCEPTIBILITY IN HCV.

Degree: UNM Biology Department, 2020, University of New Mexico

URL: https://digitalrepository.unm.edu/biol_etds/338

► Hepatitis C virus (HCV) is a global epidemic that has been increasing for decades, afflicting millions of people who inject drugs (PWID) and is… (more)

Subjects/Keywords: hepatitis; math model; sex-structured; hcv; hepatitis c virus; Biology

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shea, T. K. (2020). CAN A SEX BIAS BE A GOOD THING: MODELING SPONTANEOUS CLEARANCE AND SEXUAL SUSCEPTIBILITY IN HCV. (Masters Thesis). University of New Mexico. Retrieved from https://digitalrepository.unm.edu/biol_etds/338

Chicago Manual of Style (16^th Edition):

Shea, Tanner K. “CAN A SEX BIAS BE A GOOD THING: MODELING SPONTANEOUS CLEARANCE AND SEXUAL SUSCEPTIBILITY IN HCV.” 2020. Masters Thesis, University of New Mexico. Accessed January 17, 2021. https://digitalrepository.unm.edu/biol_etds/338.

MLA Handbook (7^th Edition):

Shea, Tanner K. “CAN A SEX BIAS BE A GOOD THING: MODELING SPONTANEOUS CLEARANCE AND SEXUAL SUSCEPTIBILITY IN HCV.” 2020. Web. 17 Jan 2021.

Vancouver:

Shea TK. CAN A SEX BIAS BE A GOOD THING: MODELING SPONTANEOUS CLEARANCE AND SEXUAL SUSCEPTIBILITY IN HCV. [Internet] [Masters thesis]. University of New Mexico; 2020. [cited 2021 Jan 17]. Available from: https://digitalrepository.unm.edu/biol_etds/338.

Council of Science Editors:

Shea TK. CAN A SEX BIAS BE A GOOD THING: MODELING SPONTANEOUS CLEARANCE AND SEXUAL SUSCEPTIBILITY IN HCV. [Masters Thesis]. University of New Mexico; 2020. Available from: https://digitalrepository.unm.edu/biol_etds/338

University of Tasmania

22. Hale, R. Behavioural virology research : the cognitive and perceptual-motor performance of chronic primarily asymptomatic Hepatitis C patients.

Degree: 1996, University of Tasmania

URL: https://eprints.utas.edu.au/19670/1/whole_HaleRowena1997_thesis.pdf

► It is commonly believed that people perform less efficiently when suffering from viral illnesses such as colds or influenza, but there is a scarcity of… (more)

Subjects/Keywords: Hepatitis C; Hepatitis C virus; Hepatitis; Viral; Virus diseases

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hale, R. (1996). Behavioural virology research : the cognitive and perceptual-motor performance of chronic primarily asymptomatic Hepatitis C patients. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/19670/1/whole_HaleRowena1997_thesis.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hale, R. “Behavioural virology research : the cognitive and perceptual-motor performance of chronic primarily asymptomatic Hepatitis C patients.” 1996. Thesis, University of Tasmania. Accessed January 17, 2021. https://eprints.utas.edu.au/19670/1/whole_HaleRowena1997_thesis.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hale, R. “Behavioural virology research : the cognitive and perceptual-motor performance of chronic primarily asymptomatic Hepatitis C patients.” 1996. Web. 17 Jan 2021.

Vancouver:

Hale R. Behavioural virology research : the cognitive and perceptual-motor performance of chronic primarily asymptomatic Hepatitis C patients. [Internet] [Thesis]. University of Tasmania; 1996. [cited 2021 Jan 17]. Available from: https://eprints.utas.edu.au/19670/1/whole_HaleRowena1997_thesis.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hale R. Behavioural virology research : the cognitive and perceptual-motor performance of chronic primarily asymptomatic Hepatitis C patients. [Thesis]. University of Tasmania; 1996. Available from: https://eprints.utas.edu.au/19670/1/whole_HaleRowena1997_thesis.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Indian Institute of Science

23. Krishnan, Sheeja M. Modeling The Population Dynamics Of Erythrocytes To Identify Optimal Drug Dosages For The Treatment Of Hepatitis C Virus Infection.

Degree: PhD, Faculty of Engineering, 2016, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/2527

► The current treatment for hepatitis C virus (HCV) infection – combination therapy with pegylated interferon and ribavirin – elicits sustained responses in only ~50% of… (more)

▼ The current treatment for hepatitis C virus (HCV) infection – combination therapy with pegylated interferon and ribavirin – elicits sustained responses in only ~50% of the patients treated. Greater cumulative exposure to ribavirin increases response to interferon-ribavirin combination therapy. A key limitation, however, is the toxic sideeffect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan in patients and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones. A small fraction of the population (~30%) with polymorphisms in the ITPA gene shows protection from ribavirin-induced anemia. The optimum dosage of ribavirin that can be tolerated is then dependent on the ITPA polymorphisms. Coupled with a previous population pharmacokinetic study, our model yields a facile formula for estimating the optimum dosage given a patient’s weight, creatinine clearance, pretreatment hemoglobin levels, and ITPA polymorphism. The reduced lifespan we predict is in agreement with independent measurements from breath tests as well as estimates derived from in vitro studies of ATP depletion. The latter estimates also agree with the extent of ATP depletion due to ribavirin that we predict from a detailed analysis of the nucleoside metabolism in erythrocytes. Our model thus facilitates in conjunction with models of viral kinetics the rational identification of treatment protocols. Our formula for optimum dose presents an avenue for personalizing ribavirin dosage. By keeping anemia tolerable, the predicted optimal dosage may improve adherence, reduce the need for drug monitoring, and increase response rates. Advisors/Committee Members: Dixit, Narendra M (advisor).

Subjects/Keywords: Hepatitis C Virus; Hepatitis C Virus Infection; Ribavirin; Erythrocytes; Ribavirin-induced Anemia; Hepatitis C Viral Infections; Ribavirin Therapy; Viral Kinetics - Mathematical Models; Hepatitis C; HCV Infection; Population Dynamics Model; Pharmacolgy

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Krishnan, S. M. (2016). Modeling The Population Dynamics Of Erythrocytes To Identify Optimal Drug Dosages For The Treatment Of Hepatitis C Virus Infection. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/2527

Chicago Manual of Style (16^th Edition):

Krishnan, Sheeja M. “Modeling The Population Dynamics Of Erythrocytes To Identify Optimal Drug Dosages For The Treatment Of Hepatitis C Virus Infection.” 2016. Doctoral Dissertation, Indian Institute of Science. Accessed January 17, 2021. http://etd.iisc.ac.in/handle/2005/2527.

MLA Handbook (7^th Edition):

Krishnan, Sheeja M. “Modeling The Population Dynamics Of Erythrocytes To Identify Optimal Drug Dosages For The Treatment Of Hepatitis C Virus Infection.” 2016. Web. 17 Jan 2021.

Vancouver:

Krishnan SM. Modeling The Population Dynamics Of Erythrocytes To Identify Optimal Drug Dosages For The Treatment Of Hepatitis C Virus Infection. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2016. [cited 2021 Jan 17]. Available from: http://etd.iisc.ac.in/handle/2005/2527.

Council of Science Editors:

Krishnan SM. Modeling The Population Dynamics Of Erythrocytes To Identify Optimal Drug Dosages For The Treatment Of Hepatitis C Virus Infection. [Doctoral Dissertation]. Indian Institute of Science; 2016. Available from: http://etd.iisc.ac.in/handle/2005/2527

University of Alberta

24. Chen, Ran. STUDIES OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS IN SCID/BEIGE-ALB/UPA CHIMERIC MICE.

Degree: PhD, Department of Medical Microbiology and Immunology, 2014, University of Alberta

URL: https://era.library.ualberta.ca/files/h702q7680

► Both hepatitis C virus (HCV) and hepatitis B virus (HBV) infections represent major global public health problems. Interferon (IFN) has been an important factor in… (more)

▼ Both hepatitis C virus (HCV) and hepatitis B virus (HBV) infections represent major global public health problems. Interferon (IFN) has been an important factor in both resolution of infection and in the treatment of both infections. Clinical data on anti-HBV and anti-HCV innate immune responses, in particular the IFN response, during natural infection in patients are limited. This is, in part, because most of patients are asymptomatic during acute stages of infection. IFN has been used to treat both HBV and HCV infections for years. Unfortunately, many patients do not respond to the IFN therapy. The reason for the variable treatment outcomes, in particular, the nonresponsiveness to IFN therapy in both HBV and HCV infections still remains unclear. In this thesis, IFN responses in HBV and HCV infections were studied using the severe combined immunodeficiency (SCID) / beige (bg) - albumin (Alb) / urokinase-type plasminogen activator (uPA) chimeric mouse model. The SCID/bg-Alb/uPA chimeric mouse model was initially reported in 2001. This model supports robust and sustained infection by clinical or tissue culture derived hepatitis viruses, such as hepatitis A virus (HAV), HBV and HCV. Evidence has shown that the antiviral response to IFN in the chimeric mouse often reflects closely the response of the identical virus in humans when treated with IFN. A time course of HCV infection was performed in SCID/bg-Alb/uPA chimeric mice to study an induced endogenous IFN response. There was a peak of interferon-stimulated gene (ISG) response at day-10 post infection, but no significant ISG upregulation was observed in long-term HCV infection in the mice. I also investigated the contributions of viral and host factors on the response of HCV infection to IFN treatment using two HCV viral strains differing in their IFN-sensitivity. These studies were performed in chimeric mice produced using three hepatocyte donors, each with distinct interleukin (IL) 28B single nucleotide polymorphisms (SNPs) at both rs12979860 and rs8099917 loci. My results showed that virus factors were the key factors determining the outcome of IFN therapy, whereas, viral interference with host janus kinase - signal transducer and activator of transcription (JAK-STAT) pathway as well as host factors, such as polymorphisms at the IL28B loci and pre-treatment levels of intrahepatic ISG expression, were less important in determining the outcome of IFN therapy in chimeric mice than they are in the patients. In addition, endogenous IFN response during the course of HBV in the SCID/bg- Alb/uPA chimeric mice was examined. No significant IFN or ISG response was detected in chimeric mice during the course of HBV infection. Since both the HBV and HCV viruses used in my studies were nonresponsive to exogenous IFN treatment in chimeric mice, the molecular mechanism of IFN nonresponsiveness of the two viruses was compared in a cohort of donor-matched chimeric mice. I found that in HBV infected chimeric mice, but not in mice infected with HCV, the JAK-STAT pathway was inhibited…

Subjects/Keywords: SCID/BEIGE-ALB/UPA CHIMERIC MOUSE MODEL; INTERFERON; HEPATITIS B VIRUS; HEPATITIS C VIRUS

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, R. (2014). STUDIES OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS IN SCID/BEIGE-ALB/UPA CHIMERIC MICE. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/h702q7680

Chicago Manual of Style (16^th Edition):

Chen, Ran. “STUDIES OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS IN SCID/BEIGE-ALB/UPA CHIMERIC MICE.” 2014. Doctoral Dissertation, University of Alberta. Accessed January 17, 2021. https://era.library.ualberta.ca/files/h702q7680.

MLA Handbook (7^th Edition):

Chen, Ran. “STUDIES OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS IN SCID/BEIGE-ALB/UPA CHIMERIC MICE.” 2014. Web. 17 Jan 2021.

Vancouver:

Chen R. STUDIES OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS IN SCID/BEIGE-ALB/UPA CHIMERIC MICE. [Internet] [Doctoral dissertation]. University of Alberta; 2014. [cited 2021 Jan 17]. Available from: https://era.library.ualberta.ca/files/h702q7680.

Council of Science Editors:

Chen R. STUDIES OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS IN SCID/BEIGE-ALB/UPA CHIMERIC MICE. [Doctoral Dissertation]. University of Alberta; 2014. Available from: https://era.library.ualberta.ca/files/h702q7680

Addis Ababa University

25. Abel, Girma. Sero-prevalence of HBV and HCV among chronic liver disease patients visiting OPD in public hospitals in Addis Ababa, Ethiopia .

Degree: 2012, Addis Ababa University

URL: http://etd.aau.edu.et/dspace/handle/123456789/2924

► Background: Hepatitis B and C viruses (HBV & HCV) are hepatotropic viruses causing viral hepatitis, chronic liver disease and hepatocellular carcinoma. Hepatitis B and C… (more)

▼ Background: Hepatitis B and C viruses (HBV & HCV) are hepatotropic viruses causing viral hepatitis, chronic liver disease and hepatocellular carcinoma. Hepatitis B and C virus infections are still major public health problems around the globe. Both of these viruses are transmitted mainly through the parenteral route and therefore a dual infection of these viruses can occur and even persists in the same patient. They are prevalent in different parts of the world including Ethiopia. In view of this, the present study was designed to determine the prevalence of HBV and HCV infection and co-infection in clinically diagnosed chronic liver disease patients who visited public hospitals of Addis Ababa. Objective: The objective of this study was to determine the prevalence of HBV and HCV infection among chronic liver disease patients who visited public hospitals of Addis Ababa, Ethiopia. Method: Hospital based cross-sectional study was conducted in three public hospitals of Addis Ababa over a period of 7 months (Nov 2010- May 2011) on clinically diagnosed chronic liver disease patients. By using questionnaire brief history and risk factors were taken from each volunteering patient. Serum samples from each volunteering patients was screened for the presence of HBsAg and anti-HCV Ab by using qualitative rapid test kits. Result: A total of 120 participants who have chronic liver disease participated in the study, where 76 of them were males and the remaining 44 were females. The age distribution range form 18-80 years and the mean age was 40.99 years ±14 SD. The overall prevalence of HBsAg and HCV was 35.8% and 22.5% respectively. The prevalence of HBsAg and anti-HCV Ab was high in age below 50 years. 2.5% of the study participants had combined HBV/HCV infection which is possible because of their common modes of transmission. Conclusion: The prevalence of HBV and HCV in chronic liver disease patients is high and dental extraction at health facility was statistically associated with HCV infection. Advisors/Committee Members: Dr. Solomon Gebre-Silassie Teklegiorgis (advisor).

Subjects/Keywords: Hepatitis B virus; Hepatitis C virus; chronic liver disease; prevalence, co-infec

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Abel, G. (2012). Sero-prevalence of HBV and HCV among chronic liver disease patients visiting OPD in public hospitals in Addis Ababa, Ethiopia . (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/2924

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Abel, Girma. “Sero-prevalence of HBV and HCV among chronic liver disease patients visiting OPD in public hospitals in Addis Ababa, Ethiopia .” 2012. Thesis, Addis Ababa University. Accessed January 17, 2021. http://etd.aau.edu.et/dspace/handle/123456789/2924.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Abel, Girma. “Sero-prevalence of HBV and HCV among chronic liver disease patients visiting OPD in public hospitals in Addis Ababa, Ethiopia .” 2012. Web. 17 Jan 2021.

Vancouver:

Abel G. Sero-prevalence of HBV and HCV among chronic liver disease patients visiting OPD in public hospitals in Addis Ababa, Ethiopia . [Internet] [Thesis]. Addis Ababa University; 2012. [cited 2021 Jan 17]. Available from: http://etd.aau.edu.et/dspace/handle/123456789/2924.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Abel G. Sero-prevalence of HBV and HCV among chronic liver disease patients visiting OPD in public hospitals in Addis Ababa, Ethiopia . [Thesis]. Addis Ababa University; 2012. Available from: http://etd.aau.edu.et/dspace/handle/123456789/2924

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne

26. Yuen, Daniel. Studying Hepatitis C virus using envelope pseudotyped lentiviral particles.

Degree: 2015, University of Melbourne

URL: http://hdl.handle.net/11343/56955

► Hepatitis C virus infection remains a significant global healthcare burden, with the sequelae of chronic HCV infection the leading indication for liver transplant worldwide. Interestingly,… (more)

▼ Hepatitis C virus infection remains a significant global healthcare burden, with the sequelae of chronic HCV infection the leading indication for liver transplant worldwide. Interestingly, between 50-80% of individuals are able to spontaneously clear acute infection without intervention, a phenomenon now thought to be linked to the rapid development of immunity. Detailed characterisation of such cases may reveal the prerequisites for an effective vaccine. During infection, the error-prone genome replication and rapid viral turnover of HCV generates a distribution of diverse sequences within infected individuals. Immune responses in the face of this diversity can be studied using pseudoviral particles, a technique exploiting the ability of retroviral capsids to functionally incorporate HCV envelope glycoproteins. The production of these HCV pseudoviral particles (HCVpp) circumvents the necessity of culturing HCV, which remains difficult. The study of anti-HCV humoral responses at the level of the individual requires the generation of pseudoviral particles bearing HCV envelopes representative of those in circulation. Such autologous HCVpp are often produced at low titre or appear to be non-functional, making antibody neutralisation assays difficult. This study examined the unique and artificial combination of HCV and retroviral gene expression occurring during pseudotyping to identify factors limiting the production of functional HCVpp. Suboptimal expression of retroviral capsid protein, the activity of intracellular antiviral mechanisms and the properties of patient-derived HCV envelope glycoproteins were found to contribute towards the low titre production of HCVpp. Although resolution of the former restrictions is possible through modifications to the process of retroviral packaging, the limited function of many patient-derived envelopes appears to be a consequence of the intrinsic sequence diversity of HCV. This issue could only be partially ameliorated by overexpression of HCV entry receptors on target hepatoma cells. Despite this shortcoming, the optimisations identified in this study were successfully employed to generate representative autologous HCVpp from envelope isolates which initially appeared non-functional. This study demonstrates possible improvements to the HCVpp system, but also Identifies other aspects of HCV envelope pseudotyping which can be further optimised to improve the overall usefulness of HCVpp as a tool for studying HCV.

Subjects/Keywords: Hepatitis C; HCV; Hepatitis C virus; pseudovirus; lentiviral pseudotyping; antibody neutralisation; viral restriction factors; quasispecies

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yuen, D. (2015). Studying Hepatitis C virus using envelope pseudotyped lentiviral particles. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/56955

Chicago Manual of Style (16^th Edition):

Yuen, Daniel. “Studying Hepatitis C virus using envelope pseudotyped lentiviral particles.” 2015. Doctoral Dissertation, University of Melbourne. Accessed January 17, 2021. http://hdl.handle.net/11343/56955.

MLA Handbook (7^th Edition):

Yuen, Daniel. “Studying Hepatitis C virus using envelope pseudotyped lentiviral particles.” 2015. Web. 17 Jan 2021.

Vancouver:

Yuen D. Studying Hepatitis C virus using envelope pseudotyped lentiviral particles. [Internet] [Doctoral dissertation]. University of Melbourne; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/11343/56955.

Council of Science Editors:

Yuen D. Studying Hepatitis C virus using envelope pseudotyped lentiviral particles. [Doctoral Dissertation]. University of Melbourne; 2015. Available from: http://hdl.handle.net/11343/56955

Penn State University

27. Croom-Perez, Tayler Jo. Expanding the Functional Proteome of an RNA Virus by Phosphorylation of a Protein Containing an Intrinsically Disordered Domain.

Degree: 2016, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/13114tjc5337

► In order for a virus to establish a chronic infection, it must maintain a dynamic equilibrium to persist against the host’s immune response without causing… (more)

▼ In order for a virus to establish a chronic infection, it must maintain a dynamic equilibrium to persist against the host’s immune response without causing acute disease. To accomplish this, the virus must participate in a multitude of complex interactions with the host. Among other virus types, many positive strand RNA viruses are known to establish persistent infections in hosts ranging from plants and livestock to humans. Compared to their eukaryotic hosts, RNA viruses have a very limited genomic capacity. With this restricted coding capacity, how an RNA virus acquires the vast functional capabilities needed for chronic infection becomes an intriguing question. Using the hepatitis C virus (HCV) as a model, we have proposed one route an RNA virus could expand its functional capacity by using a protein containing an intrinsically disordered region (IDR). The structural flexibility of a disordered region allows a protein to establish multiple interactions within the same region. This structural flexibility must be regulated though to provide specificity of function. We, and others, propose phosphorylation can regulate the conformation of an IDR. We hypothesize a ‘phosphorylation code’ exists for the HCV intrinsically disordered protein, NS5A, that regulates its myriad interactions with both host and viral proteins, allowing this protein to serve an essential role in the virus’ ability to dynamically interact with the host and establish a chronic infection. In the following studies, we have established the ability to purify the intrinsically disordered domain (IDD) of the HCV protein NS5A to a concentration and purity suitable for biophysical characterization. We have determined that the NS5A IDD has a propensity for a-helical formation. Using phosphorylation by PKA as a model, we have determined that a single phosphorylation event alters the global conformation of the NS5A IDD. This conformational change is likely inducing a more stable structure with increased a-helical content. To determine the impact of phosphorylation-induced conformational changes on the function of the NS5A protein, we have explored NS5A IDD binding to SH3 domains from several different proteins. While SH3 domains are structurally similar, we found that not only does the NS5A IDD binding to different SH3 domains differ, but PKA phosphorylation impacts the interaction of each of the SH3 domains uniquely. This study provides insight into a fundamental way binding of SH3 domains to polyproline motifs could be regulated. This exploration of the effects of PKA phosphorylation on the conformation and function of the NS5A IDD has contributed to the overall understanding of the role and regulation of intrinsically disordered proteins and provides an example of how an RNA virus with limited genetic capacity could expand its functional proteome. Advisors/Committee Members: Craig Eugene Cameron, Dissertation Advisor/Co-Advisor, Craig Eugene Cameron, Committee Chair/Co-Chair, Richard John Frisque, Committee Member, B Tracy Nixon, Committee Member, Mary Poss, Outside Member.

Subjects/Keywords: hepatitis C virus; intrinsically disordered protein; RNA virus; Phosphorylation; NMR

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Croom-Perez, T. J. (2016). Expanding the Functional Proteome of an RNA Virus by Phosphorylation of a Protein Containing an Intrinsically Disordered Domain. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13114tjc5337

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Croom-Perez, Tayler Jo. “Expanding the Functional Proteome of an RNA Virus by Phosphorylation of a Protein Containing an Intrinsically Disordered Domain.” 2016. Thesis, Penn State University. Accessed January 17, 2021. https://submit-etda.libraries.psu.edu/catalog/13114tjc5337.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Croom-Perez, Tayler Jo. “Expanding the Functional Proteome of an RNA Virus by Phosphorylation of a Protein Containing an Intrinsically Disordered Domain.” 2016. Web. 17 Jan 2021.

Vancouver:

Croom-Perez TJ. Expanding the Functional Proteome of an RNA Virus by Phosphorylation of a Protein Containing an Intrinsically Disordered Domain. [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Jan 17]. Available from: https://submit-etda.libraries.psu.edu/catalog/13114tjc5337.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Croom-Perez TJ. Expanding the Functional Proteome of an RNA Virus by Phosphorylation of a Protein Containing an Intrinsically Disordered Domain. [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/13114tjc5337

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Univerzitet u Beogradu

28. Đorđević-Vujičić, Ana I. 1979-. Selekcija specifičnih antigena virusa humane imunodeficijencije i virusa hepatitisa C za prognostičke i dijagnostičke ELISA testove korišćenjem bioinformatičkih metoda.

Degree: Farmaceutski fakultet, 2015, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:7145/bdef:Content/get

►

Medicinska biohemija / Medical biochemistry Datum odbrane: 25.06.2013.

Uvod Postojanje specifičnih i osetljivih, a samim tim, i pouzdanih imunohemijsk ih testova za detekciju brojnih virusa,… (more)

▼

Medicinska biohemija / Medical biochemistry Datum odbrane: 25.06.2013.

Uvod Postojanje specifičnih i osetljivih, a samim tim, i pouzdanih imunohemijsk ih testova za detekciju brojnih virusa, između ostalog i virusa hepatitisa C (HCV) i virusa humane imunodeficijencije (HIV), je od velikog značaja u savremenoj dijagnostici. Sličnosti velikog broja proteina virusa i humanih proteina je ozbiljan izazov pril ikom odabira specifičnog antigena za ELISA test, zbog potencijalnog unakrsnog imunskog prepoznavanja. Danas se sistemskim računarskim analizama proteinskih sekvenci mogu utvrditi karakteristične sličnosti i razlike na nivou celokupnih virusnih i humanih pr oteoma. Cilj ovog rada je bio da se iz naučne literature identifikuju sve sekvence humanih antigena koji su potencijalne mete urođenog humoralnog imunskog odgovora i da se na osnovu integrisanih bioinformatičkih analiza definišu specifični antigeni za: 1 . anti - HCV ELISA skrining testove i 2. ELISA testove kojima bi se određivala antitela koja su karakteristična za neprogresivnu HIV - 1 infekciju. Metode Studija informacionih karakteristika proteinskih sekvenci virusnih i humanih antigena je izvršena bioinfo rmatičkim programskim paketom zasnovanim na metodi informacionih spektara. Za upoređivanje sekvenci i ispitivanje homologije korišćeni su programi za lokalno i globalno poravnavanje sekvenci. Biološki klasteri u proteinskim skupovima identifikovani su prog ramima kojima se analizira obogaćenje pojmovima iz baze podataka GENE ONTOLOGY. In house testovima ispitana je specifičnost ELISA antigena čija je sekvenca definisana na osnovu informacija dobijenih integrisanim bioinformatičkim analizama Rezultati Naprav ljena je kompilacija hu manih antigena koji su reaktivni sa prirodnim autoantitelima i identifikovane su dominantne zajedničke informacione karakteristike do sada poznatih sopstvenih humanih antigena. Poklapanje ovih karakteristika sa virusnim antigenima je preduslov nespecifičnog imunskog prepoznavanja. Ispitali smo koji HCV proteini imaju značajne informacione sličnosti sa humanim autoantigenima i pokazali da su na osnovu karakteristika proteinskih sekvenci HCV antigeni NS4 i NS5 nespecifični, što je u sag lasnosti sa zaključcima iz kliničkih studija. Primenom metode informacionih spektara dizajniran je peptidni antigen za ELISA test za koji je eksperimentalno pokazano da vezuje antitela iz seruma HIV - 1 pozitivnih pacijenata, a koja su markeri neprogresivne HIV - 1 infekcije. Takođe, prisustvo ovih antitela pokazano je i u serumima novorođenih beba, što ukazuje na činjenicu da su ona deo urođenog humoralnog imunskog odgovora, što je u saglasnosti sa litreraturnim podacima. Zaključak Sistemske analize virusnog i humanog proteoma i primene bioinformatičkih metoda su od izuzetnog značaja za selekciju i dizajniranje antigena u cilju poboljšanja karakteristika ili pravljenja novih imunohemijskih testova.

Advisors/Committee Members: Spasojević-Kalimanovska, Vesna, 1956-.

Subjects/Keywords: ELISA; Natural autoantibodies; Human immunodeficiency virus; Hepatitis C virus; Bioinformatics

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Đorđević-Vujičić, A. I. 1. (2015). Selekcija specifičnih antigena virusa humane imunodeficijencije i virusa hepatitisa C za prognostičke i dijagnostičke ELISA testove korišćenjem bioinformatičkih metoda. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:7145/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Đorđević-Vujičić, Ana I 1979-. “Selekcija specifičnih antigena virusa humane imunodeficijencije i virusa hepatitisa C za prognostičke i dijagnostičke ELISA testove korišćenjem bioinformatičkih metoda.” 2015. Thesis, Univerzitet u Beogradu. Accessed January 17, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:7145/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Đorđević-Vujičić, Ana I 1979-. “Selekcija specifičnih antigena virusa humane imunodeficijencije i virusa hepatitisa C za prognostičke i dijagnostičke ELISA testove korišćenjem bioinformatičkih metoda.” 2015. Web. 17 Jan 2021.

Vancouver:

Đorđević-Vujičić AI1. Selekcija specifičnih antigena virusa humane imunodeficijencije i virusa hepatitisa C za prognostičke i dijagnostičke ELISA testove korišćenjem bioinformatičkih metoda. [Internet] [Thesis]. Univerzitet u Beogradu; 2015. [cited 2021 Jan 17]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:7145/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Đorđević-Vujičić AI1. Selekcija specifičnih antigena virusa humane imunodeficijencije i virusa hepatitisa C za prognostičke i dijagnostičke ELISA testove korišćenjem bioinformatičkih metoda. [Thesis]. Univerzitet u Beogradu; 2015. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:7145/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

29. Farhat, Rayan. Etude des mécanismes dépendants de GBF1 et impliqués dans la réplication du virus de l'hépatite C : Investigation of GBF1-dependent mechanisms involved in hepatitis C virus replication.

Degree: Docteur es, Bactério-virologie, hygiène, 2014, Université Lille II – Droit et Santé

URL: http://www.theses.fr/2014LIL2S040

► L’infection par le virus de l’hépatite C (HCV) évolue dans la plupart des cas en hépatite chronique et peut conduire à une cirrhose ou un… (more)

▼ L’infection par le virus de l’hépatite C (HCV) évolue dans la plupart des cas en hépatite chronique et peut conduire à une cirrhose ou un carcinome hépatocellulaire. Malgré les grandes avancées dans le traitement de l’hépatite C qui permettent d’inhiber ou même de bloquer l’évolution de cette infection vers la chronicité, l’absence de vaccin ainsi que sa répartition sur la surface du globe nous permet de classer cette pathologie en problème majeur de santé publique. La majorité des traitements actuels ciblent les protéines virales et leur fonction. Cependant un grand nombre de mécanismes du cycle viral de HCV reste à élucider.Comme pour la grande majorité des virus à ARN de polarité positive, la réplication de HCV a lieu dans des membranes cellulaires modifiées. Le remaniement de ces membranes est en lien étroit avec la voie de sécrétion précoce de la cellule. Il a été montré que GBF1, un facteur d’échange nucléotidique des protéines G de la famille Arf qui régulent la dynamique membranaire, est un facteur nécessaire à la réplication de HCV. L’inhibition de GBF1 par la bréfeldine A (BFA) inhibe la voie de sécrétion des protéines cellulaires néosynthétisées et inhibe aussi la réplication de HCV. Pour étudier le rôle de GBF1 pendant l’infection nous avons établi des lignées résistantes à la BFA. Deux de ces lignées étaient 100 fois plus résistantes que les lignées parentales à l’apoptose induite par la BFA, à l’inhibition de la sécrétion des protéines et à l’inhibition de l’infection par HCV. Ce phénotype était dû à une mutation ponctuelle dans le domaine catalytique sec7 de GBF1 de ces lignées. Un autre groupe de lignées était partiellement résistantes à l’inhibition de la sécrétion des protéines par la BFA tout en conservant un niveau d’infection proche de celui des lignées parentales dans les mêmes conditions. Ces résultats suggèrent que la fonction de GBF1 pendant l’infection HCV ne serait pas réduite à la régulation de la voie de sécrétion, évoquant ainsi un rôle additionnel de GBF1 nécessaire pour la réplication de HCV.Par ailleurs, nous avons pu montrer à l’aide des mutants de délétion de la protéine GBF1, que l’activité catalytique du domaine sec7 était nécessaire. Ceci suggère l’implication d’une protéine de la famille Arf dans l’activation de l’infection HCV via GBF1. L’implication de Arf dans l’infection HCV a été confirmée par la surexpression de dominants négatifs de la protéine Arf1 et par l’inhibition de l’activité de l’ArfGAP1 (régulateur des Arf) par l’inhibiteur spécifique QS11.Nous avons ensuite testé l’implication des différents Arf sensibles à l’inhibition par la BFA (Arf1, 3 ,4 et 5), dans l’infection HCV à l’aide de si-RNA. Il a été montré que ces protéines Arf possèdent des fonctions redondantes. Nos résultats confirment l’implication de Arf1 et indiquent que les 3 autres protéines sont aussi impliquées dans l’infection HCV. D’une manière intéressante, la déplétion combinée des Arf inhibe fortement l’infection HCV suggérant ainsi un rôle essentiel de certaines protéines Arf, probablement en… Advisors/Committee Members: Rouillé, Yves (thesis director).

Subjects/Keywords: GBF1; Intéraction virus-hôte; Hepatitis C virus; GBF1 inhibition

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Farhat, R. (2014). Etude des mécanismes dépendants de GBF1 et impliqués dans la réplication du virus de l'hépatite C : Investigation of GBF1-dependent mechanisms involved in hepatitis C virus replication. (Doctoral Dissertation). Université Lille II – Droit et Santé. Retrieved from http://www.theses.fr/2014LIL2S040

Chicago Manual of Style (16^th Edition):

Farhat, Rayan. “Etude des mécanismes dépendants de GBF1 et impliqués dans la réplication du virus de l'hépatite C : Investigation of GBF1-dependent mechanisms involved in hepatitis C virus replication.” 2014. Doctoral Dissertation, Université Lille II – Droit et Santé. Accessed January 17, 2021. http://www.theses.fr/2014LIL2S040.

MLA Handbook (7^th Edition):

Farhat, Rayan. “Etude des mécanismes dépendants de GBF1 et impliqués dans la réplication du virus de l'hépatite C : Investigation of GBF1-dependent mechanisms involved in hepatitis C virus replication.” 2014. Web. 17 Jan 2021.

Vancouver:

Farhat R. Etude des mécanismes dépendants de GBF1 et impliqués dans la réplication du virus de l'hépatite C : Investigation of GBF1-dependent mechanisms involved in hepatitis C virus replication. [Internet] [Doctoral dissertation]. Université Lille II – Droit et Santé 2014. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2014LIL2S040.

Council of Science Editors:

Farhat R. Etude des mécanismes dépendants de GBF1 et impliqués dans la réplication du virus de l'hépatite C : Investigation of GBF1-dependent mechanisms involved in hepatitis C virus replication. [Doctoral Dissertation]. Université Lille II – Droit et Santé 2014. Available from: http://www.theses.fr/2014LIL2S040

University of New South Wales

30. Ratnarajah , Shabnah. Protective immunity in hepatitis C virus infection.

Degree: Medical Sciences, 2013, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/52856 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11529/SOURCE01?view=true

► Primary hepatitis C virus (HCV) HCV infection is associated with viraemia which induces cellular andhumoral immune responses in the majority of individuals, regardless of subsequent… (more)

▼ Primary hepatitis C virus (HCV) HCV infection is associated with viraemia which induces cellular andhumoral immune responses in the majority of individuals, regardless of subsequent outcome. HCV-specificimmune responses have also been documented in subjects who appear to have never had infection,including in injecting drug users who are at high-risk of infection. These immune responses may beprotective, either against incident infection, or against the development of chronic infection.Minute amounts of HCV RNA at levels below detection by conventional assays have been detected insubjects who have cleared HCV infection. This occult virus infection may also occur in high risk injectingdrug users, and may therefore provide the antigenic stimulus for the observed immune responses.This study examined the presence of HCV-specific cellular immune responses in a cohort of high-risk,seronegative, aviraemic prisoners using interferon-gamma enzyme linked immunospot assays. Detailedbehavioural analyses to identify potential correlates of the presence of these immune responses, and withincident infection were undertaken. In addition, initial efforts to establish an ultra-sensitive, nested reversetranscriptionpolymerase chain reaction to detect both vegetative and replicative HCV RNA strands in highriskapparently uninfected subjects in this cohort were undertaken.A significant prevalence of HCV-specific cellular immune responses and a high rate of incident infectionwere found. There was a significant association of measured cellular immune responses with injectingcrystal methamphetamine, and surprisingly a negative association between incident infection and tattooing.There was no reduction in the incident infection rate in those with HCV-specific immunity.The studies in this thesis have demonstrated, HCV-specific cellular immune responses in a large cohort ofhigh-risk seronegative subjects. The potential association with occult infection requires further assaydevelopment and investigation. The biological significance of the immune responses in protection requiresfurther investigation. Advisors/Committee Members: Lloyd, Andrew, Medical Sciences, Faculty of Medicine, UNSW.

Subjects/Keywords: Occult virus; Hepatitis C virus; Immunity; Seronegative immune

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ratnarajah , S. (2013). Protective immunity in hepatitis C virus infection. (Masters Thesis). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/52856 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11529/SOURCE01?view=true

Chicago Manual of Style (16^th Edition):

Ratnarajah , Shabnah. “Protective immunity in hepatitis C virus infection.” 2013. Masters Thesis, University of New South Wales. Accessed January 17, 2021. http://handle.unsw.edu.au/1959.4/52856 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11529/SOURCE01?view=true.

MLA Handbook (7^th Edition):

Ratnarajah , Shabnah. “Protective immunity in hepatitis C virus infection.” 2013. Web. 17 Jan 2021.

Vancouver:

Ratnarajah S. Protective immunity in hepatitis C virus infection. [Internet] [Masters thesis]. University of New South Wales; 2013. [cited 2021 Jan 17]. Available from: http://handle.unsw.edu.au/1959.4/52856 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11529/SOURCE01?view=true.

Council of Science Editors:

Ratnarajah S. Protective immunity in hepatitis C virus infection. [Masters Thesis]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/52856 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11529/SOURCE01?view=true

		in
And / Or
		in
And / Or
		in
And / Or
		in

Open Access Theses and Dissertations