+publisher:"University of North Carolina" +contributor:("De Paris, Kristina")

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University of North Carolina

1. Giffin, Louise. Manipulation and Exploitation of the Host Cell by Kaposi's Sarcoma-Associated Herpesvirus.

Degree: Microbiology and Immunology, 2015, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:b0e6a869-b24d-4405-8884-fed4f95d62b1

► Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human gamma-herpesvirus that is the causative agent of three human malignancies: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s… (more)

▼ Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human gamma-herpesvirus that is the causative agent of three human malignancies: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV causes a lifelong infection for which there is no known cure, and the cancers associated with KSHV typically have poor prognosis and no established treatment protocol. KSHV is a large DNA virus that encodes over eighty open reading frames that have diverse functions, including viral proteins that thwart the host immune system and that alter cellular growth pathways to promote viral persistence, with the incidental effect of inducing cellular transformation. KSHV expresses several homologs of human proteins, including a homolog of interleukin 6 (hIL-6) called viral interleukin 6 (vIL-6). vIL-6 is a predominantly intracellular protein that localizes to the endoplasmic reticulum where it can signal through the gp130 subunit of the IL-6 receptor. We sought to examine how vIL-6 interacts with components of the host cell and alters host gene expression to promote vIL-6 function and induce pathogenesis. We identified hypoxia upregulated protein 1 (HYOU1) as a vIL-6-interacting partner, and found that HYOU1 supports vIL-6 protein expression and promotes vIL-6-mediated signaling, migration, and survival in endothelial cells. We also found that vIL-6 significantly upregulates the expression of genes associated with cellular movement including the adhesion factor called carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). We determined that vIL-6 increases CEACAM1 expression via STAT3 signaling, and that CEACAM1 promotes vIL-6-mediated migration of endothelial cells. Both de novo and latent KSHV infection were also found to upregulate CEACAM1. To further elucidate how KSHV modulates the cellular environment, we performed kinome profiling to identify cellular kinases that are differentially activated during latent and lytic KSHV infection in primary effusion lymphoma. Kinases regulate almost all cellular processes, and dysregulated kinase activation can drive tumorigenesis. This research may identify major pathogenic signaling pathways that are hyperactivated or shut off in KSHV-associated cancers. Further elucidating how KSHV and its encoded proteins alter the cellular environment to promote pathogenesis will identify targets for the development of novel therapeutics to treat KSHV-associated disease. Advisors/Committee Members: Giffin, Louise, Damania, Blossom, Raab-Traub, Nancy, De Paris, Kristina, Swanstrom, Ronald, Dittmer, Dirk.

Subjects/Keywords: Virology; Cytology; Immunology; School of Medicine; Department of Microbiology and Immunology

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APA (6^th Edition):

Giffin, L. (2015). Manipulation and Exploitation of the Host Cell by Kaposi's Sarcoma-Associated Herpesvirus. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:b0e6a869-b24d-4405-8884-fed4f95d62b1

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):

Giffin, Louise. “Manipulation and Exploitation of the Host Cell by Kaposi's Sarcoma-Associated Herpesvirus.” 2015. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:b0e6a869-b24d-4405-8884-fed4f95d62b1.

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

MLA Handbook (7^th Edition):

Giffin, Louise. “Manipulation and Exploitation of the Host Cell by Kaposi's Sarcoma-Associated Herpesvirus.” 2015. Web. 18 Jan 2021.

Vancouver:

Giffin L. Manipulation and Exploitation of the Host Cell by Kaposi's Sarcoma-Associated Herpesvirus. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:b0e6a869-b24d-4405-8884-fed4f95d62b1.

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

Council of Science Editors:

Giffin L. Manipulation and Exploitation of the Host Cell by Kaposi's Sarcoma-Associated Herpesvirus. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:b0e6a869-b24d-4405-8884-fed4f95d62b1

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

University of North Carolina

2. Potempa, Marc. Mechanisms Regulating HIV-1 Protease Activity.

Degree: Microbiology and Immunology, 2015, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:0f7ef394-0dc8-43d8-92d7-cd6e230029b7

► The Human Immunodeficiency Virus Type 1 (HIV-1) Protease (PR) has no direct involvement in the early steps of HIV-1 replication. Nonetheless, it is the timely… (more)

▼ The Human Immunodeficiency Virus Type 1 (HIV-1) Protease (PR) has no direct involvement in the early steps of HIV-1 replication. Nonetheless, it is the timely and ordered processing of the viral structural proteins by the HIV-1 PR during virion maturation that facilitates the successful completion of virus entry, reverse transcription, and integration. Though a considerable amount of research has been devoted to deciphering how the enzyme prepares a virus particle for infection, the mechanisms regulating its activities continue to remain incompletely defined. RNA serves as one putative regulatory factor, since efficient processing of the maturation intermediate p15NC requires RNA in vitro. Though previously believed relevant to only p15NC cleavage, I demonstrate that RNA enhances HIV-1 proteolysis reactions in a substrate-independent manner. The increased catalytic activity of the HIV-1 PR results from a direct interaction between RNA and the enzyme, with the magnitude of the effect dependent upon the size of the RNA molecule. Large (>400 base) RNAs accelerated proteolytic processing by over 100-fold under near-physiological conditions. This considerable change stemmed from both improved substrate recognition (Km) and turnover rate (kcat). Variability in amino acid sequence also guides HIV-1 PR activity. However, the absence of any overt patterns across HIV-1 cleavage sites has complicated the delineation of why these differences result in diverse processing efficiencies. To address this question, I generated the largest-to-date dataset of globular proteins cleaved by the HIV-1 PR in near-physiological conditions. From these data, I unravel a number of site-specific processing requirements, and identify potentially important relationships shared between multiple cleavage sites. These results additionally enabled the formation of a preliminary conceptual model for explaining processing site amino acid composition. Advisors/Committee Members: Potempa, Marc, Swanstrom, Ronald, Lemon, Stanley, Margolis, David, De Paris, Kristina, Carter, Charles.

Subjects/Keywords: Virology; Molecular biology; Biochemistry; School of Medicine; Department of Microbiology and Immunology

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

APA (6^th Edition):

Potempa, M. (2015). Mechanisms Regulating HIV-1 Protease Activity. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:0f7ef394-0dc8-43d8-92d7-cd6e230029b7

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):

Potempa, Marc. “Mechanisms Regulating HIV-1 Protease Activity.” 2015. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:0f7ef394-0dc8-43d8-92d7-cd6e230029b7.

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

MLA Handbook (7^th Edition):

Potempa, Marc. “Mechanisms Regulating HIV-1 Protease Activity.” 2015. Web. 18 Jan 2021.

Vancouver:

Potempa M. Mechanisms Regulating HIV-1 Protease Activity. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:0f7ef394-0dc8-43d8-92d7-cd6e230029b7.

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

Council of Science Editors:

Potempa M. Mechanisms Regulating HIV-1 Protease Activity. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:0f7ef394-0dc8-43d8-92d7-cd6e230029b7

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

University of North Carolina

3. Arrildt, Kathryn. Phenotypic and Genotypic Features of Macrophage Tropism in HIV-1.

Degree: Microbiology and Immunology, 2016, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:650b39d7-9d1e-4d34-8e5b-a219db67813e

► HIV-1 preferentially attaches and enters specific cell types by recognizing cell-specific receptors. HIV-1 typically targets memory CD4+ T cells by restricting attachment to cells expressing… (more)

▼ HIV-1 preferentially attaches and enters specific cell types by recognizing cell-specific receptors. HIV-1 typically targets memory CD4+ T cells by restricting attachment to cells expressing high CD4 densities and by using the CCR5 coreceptor. HIV-1 can adapt to enter CD4+ naïve T cells by evolving to use CXCR4 in addition to CCR5. Alternatively, HIV-1 can adapt infecting macrophages by enhancing the entry using low CD4 densities. Early classification confusion and the lack of a reproducible, high-throughput method to assess cellular tropism has hindered robust identification and characterization of macrophage tropism. We developed cellular tropism assays using a novel cell line to perform both high-throughput identification screens and detailed analyses of receptor and coreceptor interactions. Clarified definitions of cellular tropism enabled us to probe the mechanism and consequences of evolving macrophage tropism through genotypic and phenotypic characterizations of subject-matched T-tropic and M-tropic env genes. M-tropic Env proteins are mostly indistinguishable from T-tropic Env proteins, except for subtle differences in the CD4-binding site (CD4bs) revealed by differences in interactions with CD4, competitive inhibition by soluble CD4, anti-CD4bs antibody sensitivity, and the ability of CD4-binding proximal residues to affect CD4 usage. CD4 usage is highly correlated with entry of monocyte-derived macrophages over a continuous range, making CD4 usage a useful proxy for macrophage tropism. Other stages of binding and entry are not major factors in the evolution of macrophage tropism and M-tropic Env proteins are not generally sensitive to antibodies. Nor does the antibody environment appear as a major selective pressure on the evolution of macrophage tropism. The genetic determinants are complex; evolving macrophage tropism requires unique constellations of amino acid substitutions at distal locations in the Env protein. However, substitutions of bulkier, more hydrophobic amino acid residues tend to accumulate in the V5 region of the Env protein. The true genetic determinants of macrophage tropism are still unknown, but we have begun to identify features to help identify new M-tropic viruses, which is an essential part of unraveling the greater mysteries of macrophage tropism. Advisors/Committee Members: Arrildt, Kathryn, Swanstrom, Ronald, de Paris, Kristina, De Silva, Aravinda Manu, Su, Lishan, Moorman, Nathaniel.

Subjects/Keywords: School of Medicine; Department of Microbiology and Immunology

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

APA (6^th Edition):

Arrildt, K. (2016). Phenotypic and Genotypic Features of Macrophage Tropism in HIV-1. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:650b39d7-9d1e-4d34-8e5b-a219db67813e

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):

Arrildt, Kathryn. “Phenotypic and Genotypic Features of Macrophage Tropism in HIV-1.” 2016. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:650b39d7-9d1e-4d34-8e5b-a219db67813e.

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

MLA Handbook (7^th Edition):

Arrildt, Kathryn. “Phenotypic and Genotypic Features of Macrophage Tropism in HIV-1.” 2016. Web. 18 Jan 2021.

Vancouver:

Arrildt K. Phenotypic and Genotypic Features of Macrophage Tropism in HIV-1. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:650b39d7-9d1e-4d34-8e5b-a219db67813e.

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

Council of Science Editors:

Arrildt K. Phenotypic and Genotypic Features of Macrophage Tropism in HIV-1. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:650b39d7-9d1e-4d34-8e5b-a219db67813e

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

University of North Carolina

4. Goheen, Morgan. Iron Deficiency Anemia and the Pathogenesis of Falciparum Malaria.

Degree: Microbiology and Immunology, 2016, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:6b016a5e-3a05-4c06-b4e5-f1b73bdc9292

► Anemia, primarily iron deficiency anemia (IDA), affects up to 50% of pregnant women and 40% of preschool children in the developing world, significantly impacting perinatal… (more)

▼ Anemia, primarily iron deficiency anemia (IDA), affects up to 50% of pregnant women and 40% of preschool children in the developing world, significantly impacting perinatal and developmental health. However, clinical studies have found (1) iron deficiency protects from malaria, and (2) administration of iron to iron deficient individuals may increase the risk of malaria, thus complicating universal iron supplementation recommendations in malaria-endemic areas. Our lab developed an in vitro model, obtaining red blood cells (RBCs) from IDA or healthy donors at UNC, to study mechanisms of malaria-associated IDA protection and iron treatment risk. We demonstrated decreased P.falciparum invasion and growth in IDA RBCs and increased infection susceptibility in young RBCs and reticulocytes. Given iron is essential for the parasite, it was previously thought iron deficiency inhibited malaria through starvation. However, IDA also limits erythropoiesis and induces physiologic RBC changes. Our UNC-based studies thus generated a novel and paradigm-shifting hypothesis – namely that changes in RBC properties and the RBC population structure drive IDA resistance to and iron supplementation risk for malaria. Our next objective was to evaluate this hypothesis in pregnant women and children from a malaria-endemic area, via comprehensive longitudinal examination of P.falciparum pathogenesis in RBCs drawn from iron deficient Gambian children and pregnant women before, during, and after iron supplementation. RBCs were collected from 135 children and 165 pregnant women throughout 12 weeks of iron supplementation and used in flow cytometry-based in vitro assays. Our results demonstrate P.falciparum erythrocytic stage growth in vitro is low at baseline, correlating with hemoglobin levels and mean corpuscular volume. We also determined parasite growth increases during supplementation, using RBCs from both children and pregnant women. Additionally, we found reduced parasite invasion in RBCs from iron deficient Gambian children, which increases during iron supplementation. The elevated growth rates following iron supplementation paralleled increases in circulating reticulocytes and other markers of young RBCs, kinetics of which correlate with overall increased erythropoiesis. We conclude malaria growth in vitro corresponds with elevated erythropoiesis, an inevitable consequence of iron supplementation. Our findings imply iron supplementation in malarious regions should be accompanied by effective preventative measures against falciparum malaria. Advisors/Committee Members: Goheen, Morgan, De Paris, Kristina, Cerami, Carla, Meshnick, Steven R., Kasthuri, Raj, Kawula, Thomas, Cohen, Myron.

Subjects/Keywords: School of Medicine; Department of Microbiology and Immunology

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

APA (6^th Edition):

Goheen, M. (2016). Iron Deficiency Anemia and the Pathogenesis of Falciparum Malaria. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:6b016a5e-3a05-4c06-b4e5-f1b73bdc9292

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):

Goheen, Morgan. “Iron Deficiency Anemia and the Pathogenesis of Falciparum Malaria.” 2016. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:6b016a5e-3a05-4c06-b4e5-f1b73bdc9292.

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

MLA Handbook (7^th Edition):

Goheen, Morgan. “Iron Deficiency Anemia and the Pathogenesis of Falciparum Malaria.” 2016. Web. 18 Jan 2021.

Vancouver:

Goheen M. Iron Deficiency Anemia and the Pathogenesis of Falciparum Malaria. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:6b016a5e-3a05-4c06-b4e5-f1b73bdc9292.

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

Council of Science Editors:

Goheen M. Iron Deficiency Anemia and the Pathogenesis of Falciparum Malaria. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:6b016a5e-3a05-4c06-b4e5-f1b73bdc9292

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

University of North Carolina

5. Watkins, Richard. Role of HIV-1 Nef and Vpu in viral replication and CD4+ T cell depletion.

Degree: Microbiology and Immunology, 2014, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:64424cc4-607e-4b79-8981-af428ec1c475

► HIV-1, within its 9-gene genome, encodes a set of accessory proteins regarded as nonessential for in vitro replication, but that are critical for optimal viral… (more)

▼ HIV-1, within its 9-gene genome, encodes a set of accessory proteins regarded as nonessential for in vitro replication, but that are critical for optimal viral replication in vivo. Specifically, Nef and Vpu, two proteins with some overlap in function, have been implicated in robust viral replication and disease progression. As part of my dissertation I used an LAI with a simple frame-shift in nef, ablating the expression of Nef, and demonstrated the in vivo pressure to restore the nef ORF. I went on to show, that the protein resulting from the reopening of the nef ORF was defective for CD4 downmodulation. Mice infected with LAI containing these in vivo generated nefs displayed reduced viral loads and the CD4 depletion compared to mice infected with wild type LAI. When the infections with a more severally defective nef that was irreversibly inactivated are compared to infections with LAI containing Nefs defective for CD4 downmodulation, I found that nearly 50% of the pathogenic phenotype of wild type LAI could be attributed to Nef's ability to downmodulate surface expression of CD4. I also examined the role that Vpu plays in replication and CD4+ T cell depletion during an LAI infection in BLT-humanized mice. These investigations demonstrate that Vpu is required for rapid CD4+ T cell depletion and high viral loads. Of interest is that Vpu-defective HIV-1 expressing no Vpu and HIV-1 expressing Nef specifically lacking the ability to downmodulate CD4 have strikingly similar replicative and pathogenic phenotypes. I also examined the contribution nef makes to high viral loads and CD4+ T cell depletion during the infection of the CCR5-tropic virus, HIV-1 JRCSF. Mice infected with JRCSF expressing defective nefs have lower viral loads and maintain a higher percentage of their CD4+ T cells than mice infected with wild type JRCSF. I also demonstrate that like LAI, JRCSF expressing a frame-shifted nef restores the nef ORF. I show in this dissertation that the Nef produced by one of these in vivo-generated nef mutants is also specifically defective for CD4 downregulation. I also performed a longitudinal analysis of peripheral blood CD8+ T cell activation to demonstrate that Nef is required for increased T cell activation during JRCSF infection. My dissertation demonstrates that the high viral loads and CD4+ T cell depletion seenduring HIV infection depends on the presence of Nef and Vpu. Specifically, Nef has a critical role in determining the outcome of infection. The presence of Nef is required for immune activation, which may explain differences in pathogenic outcomes. Advisors/Committee Members: Watkins, Richard, Garcia-Martinez, J. Victor, Swanstrom, Ronald, De Paris, Kristina, Margolis, David, Baric, Ralph S..

Subjects/Keywords: Virology; Microbiology; Immunology; School of Medicine; Department of Microbiology and Immunology

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APA (6^th Edition):

Watkins, R. (2014). Role of HIV-1 Nef and Vpu in viral replication and CD4+ T cell depletion. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:64424cc4-607e-4b79-8981-af428ec1c475

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):

Watkins, Richard. “Role of HIV-1 Nef and Vpu in viral replication and CD4+ T cell depletion.” 2014. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:64424cc4-607e-4b79-8981-af428ec1c475.

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

MLA Handbook (7^th Edition):

Watkins, Richard. “Role of HIV-1 Nef and Vpu in viral replication and CD4+ T cell depletion.” 2014. Web. 18 Jan 2021.

Vancouver:

Watkins R. Role of HIV-1 Nef and Vpu in viral replication and CD4+ T cell depletion. [Internet] [Thesis]. University of North Carolina; 2014. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:64424cc4-607e-4b79-8981-af428ec1c475.

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

Council of Science Editors:

Watkins R. Role of HIV-1 Nef and Vpu in viral replication and CD4+ T cell depletion. [Thesis]. University of North Carolina; 2014. Available from: https://cdr.lib.unc.edu/record/uuid:64424cc4-607e-4b79-8981-af428ec1c475

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

University of North Carolina

6. Saladyanant, Thatsanee. HPV and Oral Innate Immunity: A Role for E5.

Degree: 2015, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:09fb9963-69c6-4026-8419-806a1d031c01

► High (HR) and low-risk (LR) Human Papillomaviruses (HPVs) are known as the causative agents for benign and malignant lesions in the head and neck region.… (more)

▼ High (HR) and low-risk (LR) Human Papillomaviruses (HPVs) are known as the causative agents for benign and malignant lesions in the head and neck region. HR-and LR- infections differentially modify signal transduction and host immune responses. Of the HPV oncoproteins, HPVE5 is a small hydrophobic protein whose role is undefined in oral keratinocytes. We hypothesized that HR and LR-HPVE5 proteins differentially impact oral signal transduction, type I interferon responses, and cell differentiation processes. Our long-term goal is to elucidate the mechanisms of HPV integration. We generated pCMV plasmid vectors containing; whole genomes with E5 (HR-HPV16WT) or with E5 deleted (HPV16ΔE5), HPV16E5-tagged, transcribed but un-translated HPV16E5 (in the context of the whole genome or overexpressed), and LR-HPV6E5 genome. All constructs were transfected into oral keratinocytes and human primary foreskin keratinocytes. By growing cells on monolayer system, higher expression of phospho-p38 MAPK, phospho-MEK1/2 and phospho-Erk1/2 proteins were detected with HR-HPV16E5 but not with LR-HPV6E5 over-expression. Phospho-AKT and phospho-JNK levels were not different between HR and LR. The HR-E5 mRNA maintained MAPK activation implying a role for E5 transcripts in MAPK modulation. This effect was diminished in the absence of EGF and in the presence of terminal differentiation. HR-HPV16E5 demonstrated higher interferon promoter activity and ISG expression (ISG54 and 2’5’ OAS) that was inhibited with Cox-2 inhibitor. The HPV16ΔE5 behaved similarly to LR-HPV6E5. HPV16E5 also showed the suppressive effect on E6 splicing. By growing cells in organotypic raft culture, HPV16WT and HPV16E5 induced hyper-proliferation, activated spinous differentiation, and delayed terminal differentiation. HPV16E5 induced higher STAT1, and STAT3 expression compared to HPV6E5. In conclusion, cell proliferation and activation of intracellular immune responses are critical to transformation of oral keratinocytes and subsequent cancer development. HR-HPV16E5 increased MAPK proliferation signals, enhanced type I interferon responses and STAT3, delayed terminal differentiation, enhanced spinous differentiation, and control E6 and E7 expression whereas LR-HPV6E5 and HPV16ΔE5 barely did. In summary, HR-HPV16E5 may be a key facilitator of oncogenic progression in the head and neck region while LR-HPV6E5 is not. Advisors/Committee Members: Saladyanant, Thatsanee, Webster-Cyriaque, Jennifer, Raab-Traub, Nancy, Arnold, Roland, De Paris, Kristina, Heise, Mark, Webster-Cyriaque, Jennifer.

Subjects/Keywords: Virology; Dentistry; School of Dentistry; Oral and Craniofacial Biomedicine PhD Program

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

APA (6^th Edition):

Saladyanant, T. (2015). HPV and Oral Innate Immunity: A Role for E5. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:09fb9963-69c6-4026-8419-806a1d031c01

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):

Saladyanant, Thatsanee. “HPV and Oral Innate Immunity: A Role for E5.” 2015. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:09fb9963-69c6-4026-8419-806a1d031c01.

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

MLA Handbook (7^th Edition):

Saladyanant, Thatsanee. “HPV and Oral Innate Immunity: A Role for E5.” 2015. Web. 18 Jan 2021.

Vancouver:

Saladyanant T. HPV and Oral Innate Immunity: A Role for E5. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:09fb9963-69c6-4026-8419-806a1d031c01.

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

Council of Science Editors:

Saladyanant T. HPV and Oral Innate Immunity: A Role for E5. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:09fb9963-69c6-4026-8419-806a1d031c01

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

University of North Carolina

7. Honeycutt, Jenna. Investigation of the Role of Myeloid and T Cells in Human Immunodeficiency Virus (HIV) Infection and Persistence in Vivo.

Degree: Microbiology and Immunology, 2015, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:fc84b1db-7d13-44fc-96bf-168092a071df

► Human immunodeficiency virus (HIV) infection is the causative agent of AIDS and readily infects CD4+ T cells. I have characterized a humanized T cell only… (more)

▼ Human immunodeficiency virus (HIV) infection is the causative agent of AIDS and readily infects CD4+ T cells. I have characterized a humanized T cell only mouse (ToM) model that I have used to better understand pathogenesis of HIV infection in T cells. HIV infection is maintained over the lifetime of these animals, and viral replication is controlled using antiretroviral therapy. I have also demonstrated that latent HIV infection is readily established in ToM and that discontinuation of ART in these mice results in rapid viral rebound. These observations demonstrated that the presence of human myeloid-derived cells is not necessary for effective HIV replication or for HIV persistence in vivo. However, T cells are not the only targets of infection, and previous studies have indicated that macrophages represent another target for infection as these cells express the cell surface receptors for HIV entry, CD4 and CCR5. Recent evidence that presence of virus in macrophages may be attributed to phagocytosis of T cells by macrophages and not to productive infection has highlighted the need for a careful re-evaluation of HIV infection of macrophages. I characterized the susceptibility of NOD/SCID mice reconstituted with human CD34+ stem cells to infection with HIV. These mice are devoid of human (and mouse) T cells, and I established that replication in this model occurs in tissue macrophages. I have established that only macrophage-tropic HIV isolates are able to replicate in these mice, HIV is present systemically, and viral replication is sustained over time. Since the only targets for HIV infection present in these mice are of myeloid origin, they have been designated as myeloid-only mice (MoM). Treatment with antiretroviral therapy in MoM results in the rapid depletion of virus in plasma and tissues. Removal of therapy resulted in delayed viral rebound, demonstrating that macrophages are a source of viral rebound after ART-interruption. Overall, I present herein two new and complementary models of HIV infection: ToM and MoM. These two models along with the humanized bone marrow/liver/thymus (BLT) mouse model, which is reconstituted with human T and myeloid cells, will allow us to establish definitive roles for T cells and myeloid cells in multiple areas of research including mucosal transmission, viral persistence, and new therapies for treatment or for cure. Advisors/Committee Members: Honeycutt, Jenna, Garcia-Martinez, J. Victor, De Paris, Kristina, Eron, Joseph, Murdoch, David, Wan, Yisong, Collins, Edward.

Subjects/Keywords: Virology; Immunology; Microbiology; School of Medicine; Department of Microbiology and Immunology

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

APA (6^th Edition):

Honeycutt, J. (2015). Investigation of the Role of Myeloid and T Cells in Human Immunodeficiency Virus (HIV) Infection and Persistence in Vivo. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:fc84b1db-7d13-44fc-96bf-168092a071df

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):

Honeycutt, Jenna. “Investigation of the Role of Myeloid and T Cells in Human Immunodeficiency Virus (HIV) Infection and Persistence in Vivo.” 2015. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:fc84b1db-7d13-44fc-96bf-168092a071df.

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

MLA Handbook (7^th Edition):

Honeycutt, Jenna. “Investigation of the Role of Myeloid and T Cells in Human Immunodeficiency Virus (HIV) Infection and Persistence in Vivo.” 2015. Web. 18 Jan 2021.

Vancouver:

Honeycutt J. Investigation of the Role of Myeloid and T Cells in Human Immunodeficiency Virus (HIV) Infection and Persistence in Vivo. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:fc84b1db-7d13-44fc-96bf-168092a071df.

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

Council of Science Editors:

Honeycutt J. Investigation of the Role of Myeloid and T Cells in Human Immunodeficiency Virus (HIV) Infection and Persistence in Vivo. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:fc84b1db-7d13-44fc-96bf-168092a071df

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

University of North Carolina

8. Parobek, Christian. Dissecting the Effects of Selective Pressures on the Genomes of Co-endemic Plasmodium vivax and Plasmodium falciparum in Cambodia.

Degree: 2016, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:c98b7fd0-9ac8-4170-97e4-523bfd1cf634

► Each year, the malaria parasites Plasmodium vivax and Plasmodium falciparum together infect hundreds of millions of people and cause hundreds of thousands of deaths. In… (more)

▼ Each year, the malaria parasites Plasmodium vivax and Plasmodium falciparum together infect hundreds of millions of people and cause hundreds of thousands of deaths. In Cambodia, these two parasites are co-endemic, transmitted by the same vectors, and cause disease in the same populations. Recently, pointed efforts have been made in western Cambodia to eliminate malaria. This selective pressure provides a natural experiment that enables direct comparison of P. vivax and P. falciparum populations. Here, we explore the genetic similarities and differences between co-endemic P. vivax and P. falciparum from Cambodia through three questions to be answered. First, we conducted a pilot study in which we deep sequenced two important antigens - pvmsp1 and pvcsp - from 48 P. vivax clinical isolates and explored the contrasting population genetics of these two antigens. We discovered that, in population genetic studies, marker choice has a profound effect on study outcomes, and that P. vivax and P. falciparum orthologs can host very different signatures of selection. Next, through whole-genome sequencing of 80 P. falciparum isolates, we found that population substructuring associates with artemisinin-combination therapy partner-drug in vitro IC50 and with clinical outcomes. This finding suggests that the P. falciparum population has in part responded to selective pressures with complex demographic changes. Finally, we whole-genome sequenced 70 sympatric P. vivax isolates. We found that, in spite of control efforts and in contrast to P. falciparum, the genetic diversity within the P. vivax population remains high and has been more rapidly expanding. We identified a minority of orthologous loci that have opposite signatures of selection in P. vivax and P. falciparum. Surprisingly, we found evidence of several strong and recent selective sweeps within the P. vivax population at transcriptional regulatory loci. This finding suggests that P. vivax may rely on a nuanced response to selective pressure, modulating transcript levels as a means to maintain population resilience. Advisors/Committee Members: Parobek, Christian, Juliano, Jonathan, Meshnick, Steven R., Bailey, Jeffrey, De Paris, Kristina, Jones, Corbin, Juliano, Jonathan, Sethupathy, Praveen.

Subjects/Keywords: School of Medicine; Curriculum in Genetics and Molecular Biology

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

APA (6^th Edition):

Parobek, C. (2016). Dissecting the Effects of Selective Pressures on the Genomes of Co-endemic Plasmodium vivax and Plasmodium falciparum in Cambodia. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:c98b7fd0-9ac8-4170-97e4-523bfd1cf634

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):

Parobek, Christian. “Dissecting the Effects of Selective Pressures on the Genomes of Co-endemic Plasmodium vivax and Plasmodium falciparum in Cambodia.” 2016. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:c98b7fd0-9ac8-4170-97e4-523bfd1cf634.

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

MLA Handbook (7^th Edition):

Parobek, Christian. “Dissecting the Effects of Selective Pressures on the Genomes of Co-endemic Plasmodium vivax and Plasmodium falciparum in Cambodia.” 2016. Web. 18 Jan 2021.

Vancouver:

Parobek C. Dissecting the Effects of Selective Pressures on the Genomes of Co-endemic Plasmodium vivax and Plasmodium falciparum in Cambodia. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:c98b7fd0-9ac8-4170-97e4-523bfd1cf634.

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

Council of Science Editors:

Parobek C. Dissecting the Effects of Selective Pressures on the Genomes of Co-endemic Plasmodium vivax and Plasmodium falciparum in Cambodia. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:c98b7fd0-9ac8-4170-97e4-523bfd1cf634

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

University of North Carolina

9. Tsai, Perry. Investigation of HIV cure strategies in vivo in BLT humanized mice.

Degree: Microbiology and Immunology, 2016, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:bd98e8a0-b444-4b11-9fea-002d6eb1922b

► There is no cure yet for HIV. The development of HIV cure strategies will be accelerated by the use of animal models for HIV infection… (more)

▼ There is no cure yet for HIV. The development of HIV cure strategies will be accelerated by the use of animal models for HIV infection and treatment. Here, we investigated several HIV cure strategies in BLT humanized mice. First, we sought to explore the use of CCR5delta32 transplant to cure HIV-infected BLT mice. We found that CCR5delta32 stem cells engrafted in NSG mice and rendered them resistant to HIV infection. However, we were not able to successfully engraft CCR5delta32 cells in infected, suppressed mice. Alternatively, a cure might be achieved by reversing HIV latency, so we tested a latency-reversing agent: histone deacetylase inhibitor panobinostat. Panobinostat treatment resulted in increased histone acetylation in BLT mice, but did not significantly change levels of HIV cell-associated RNA, DNA, or latently infected cells in infected, suppressed BLT mice. Such an approach may require combination with other latency-reversing or cell-killing strategies. Next, we investigated the ability of CD8+ T cells to control HIV infection in BLT mice generated from donors with protective HLA alleles. While these mice did not control wildtype infection, several mice were able to control infection with a nef-deleted virus; and peak viral loads and average viral loads were significantly lower in two cohorts infected with nef-deleted virus. We also detected functional, HLA-restricted, HIV-specific CD8+ T cells in the mice; and viremia increased rapidly in several mice after CD8-depletion. These studies suggest that CD8+ T cells are able to control infection in BLT mice only with nef-deficient virus. A targeted immunological agent may be necessary for CD8+ T cells to kill infected cells. We tested a novel CD19xCD3 dual affinity retargeting (DART) molecule for redirected lysis in BLT mice. DART molecule administration resulted in profound depletion of CD19+ cells in both peripheral blood and tissues, and this depletion was dependent on the presence of CD8+ T cells. Overall, I present herein results from four approaches in HIV cure — allogeneic transplant, latency reversal, CD8+ T cell control, redirected lysis — in BLT humanized mice. This work represents significant progress in the development of BLT humanized mice for use in research toward an HIV cure. Advisors/Committee Members: Tsai, Perry, Garcia-Martinez, J. Victor, De Paris, Kristina, Eron, Joseph, Goonetilleke, Nilu, Miao, Edward, Serody, Jonathan.

Subjects/Keywords: School of Medicine; Department of Microbiology and Immunology

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Tsai, P. (2016). Investigation of HIV cure strategies in vivo in BLT humanized mice. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:bd98e8a0-b444-4b11-9fea-002d6eb1922b

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):

Tsai, Perry. “Investigation of HIV cure strategies in vivo in BLT humanized mice.” 2016. Thesis, University of North Carolina. Accessed January 18, 2021. https://cdr.lib.unc.edu/record/uuid:bd98e8a0-b444-4b11-9fea-002d6eb1922b.

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

MLA Handbook (7^th Edition):

Tsai, Perry. “Investigation of HIV cure strategies in vivo in BLT humanized mice.” 2016. Web. 18 Jan 2021.

Vancouver:

Tsai P. Investigation of HIV cure strategies in vivo in BLT humanized mice. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2021 Jan 18]. Available from: https://cdr.lib.unc.edu/record/uuid:bd98e8a0-b444-4b11-9fea-002d6eb1922b.

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

Council of Science Editors:

Tsai P. Investigation of HIV cure strategies in vivo in BLT humanized mice. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:bd98e8a0-b444-4b11-9fea-002d6eb1922b

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

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Open Access Theses and Dissertations