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Investigating The Roles Of Nedd4.2s And Nef In The Release And Replication Of Hiv-1: A Dissertation, Eric R. Weiss Sep 2012

Investigating The Roles Of Nedd4.2s And Nef In The Release And Replication Of Hiv-1: A Dissertation, Eric R. Weiss

GSBS Dissertations and Theses

Replication of HIV-1 requires the assembly and release of mature and infectious viral particles. In order to accomplish this goal, HIV-1 has evolved multiple methods to interact with the host cell. HIV-1 recruits the host cell ESCRT machinery to facilitate the release of nascent viral particles from the host cell membrane. Recruitment of these cellular factors is dependent on the presence of short motifs in Gag referred to as Late-domains. Deletion or mutation of these domains results in substantial decrease in the release of infectious virions. However, previously published work has indicated that over-expression of the E3 ubiquitin ligase, NEDD4 ...


Hepatitis C Virus Non-Structural Protein 3/4a: A Tale Of Two Domains: A Dissertation, Cihan Aydin Aug 2012

Hepatitis C Virus Non-Structural Protein 3/4a: A Tale Of Two Domains: A Dissertation, Cihan Aydin

GSBS Dissertations and Theses

Two decades after the discovery of the Hepatitis C Virus (HCV), Hepatitis C infection still persists to be a global health problem. With the recent approval of the first set of directly acting antivirals (DAAs), the rate of sustained viral response for HCV-infected patients increased significantly. However, a complete cure has not been found yet. Drug development efforts primarily target NS3/4A protease, bifunctional serine protease-RNA helicase of HCV. HCV NS3/4A is critical in viral function; protease domain processes the viral polyprotein and helicase domain aids replication of HCV genome by unwinding double stranded RNA transcripts produced by NS5B ...


Studies On Cellular Host Factors Involved In The Hiv-1 Life Cycle: A Dissertation, Anna Kristina Serquiña Aug 2012

Studies On Cellular Host Factors Involved In The Hiv-1 Life Cycle: A Dissertation, Anna Kristina Serquiña

GSBS Dissertations and Theses

Human Immunodeficiency Virus Type 1 (HIV-1) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), currently the leading cause of death from infectious diseases. Since HIV-1 co-opts the host cellular machinery, the study of cellular factors involved is a rational approach in discovering novel therapeutic targets for AIDS drug development. In this thesis, we present studies on two such proteins. APOBEC3G is from the family of cytidine deaminases known to keep endogenous retroviruses and retrotransposons at bay to maintain stability of the human genome. APOBEC3G targets Vif-deficient HIV-1 particles and renders them noninfectious, partially through deaminase-dependent hypermutation of the provirus ...


Rna-Sensing Pattern Recognition Receptors And Their Effects On T-Cell Immune Responses: A Dissertation, Rachel F. Madera Jul 2012

Rna-Sensing Pattern Recognition Receptors And Their Effects On T-Cell Immune Responses: A Dissertation, Rachel F. Madera

GSBS Dissertations and Theses

Virus infection is sensed by the innate immune system through germline encoded pattern recognition receptors (PRRs). Toll-like receptors (TLRs), retinoic acid-inducible gene-I-like receptors (RLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs) serve as PRRs that recognize different viral components. Microbial nucleic acids such as Ribonucleic acid (RNA) are important virus-derived pathogen-associated molecular patterns (PAMPs) to be recognized by PRRs. Virus recognition may occur at multiple stages of the viral life cycle. Replication intermediates such as single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) are detected by the RNA-sensing PRRs that initiate innate and adaptive immune responses. Triggering of the innate immune system ...


Innate Signaling Pathways In The Maintenance Of Serological Memory: A Dissertation, Forum M. Raval Jun 2012

Innate Signaling Pathways In The Maintenance Of Serological Memory: A Dissertation, Forum M. Raval

GSBS Dissertations and Theses

Long-term antiviral antibody responses provide protection from re-infection and recurrence of persistent viruses. Using a polyomavirus (PyV) mouse model, our lab has shown that MyD88-deficient mice generate low levels of virus-specific IgG after the acute phase of infection and that these IgG responses have a skewed isotype distribution with low levels of IgG2a/c. Moreover MyD88-deficient mice have reduced numbers of long-lived plasma cells in the bone marrow. These studies suggest an important role of MyD88-mediated signaling in long-term antiviral responses. Our lab has shown that T cell-deficient mice can also maintain long-term virus-specific IgG responses following PyV infection. The ...


Transcriptional Regulation Of The Interleukin-8 Promoter By Multiple Dengue Viral Proteins: A Dissertation, Jacob M. Collins May 2012

Transcriptional Regulation Of The Interleukin-8 Promoter By Multiple Dengue Viral Proteins: A Dissertation, Jacob M. Collins

GSBS Dissertations and Theses

Dengue virus (DENV) causes over 500,000 infections annually with a spectrum of clinical diseases ranging from subclinical infection to dengue, a mild febrile illness, to life-threatening severe dengue. Vascular leakage without endothelial cell damage is the hallmark symptom of severe dengue illness and is proposed to be directly mediated by soluble inflammatory mediators IL-8 and TNFα. IL-8 production occurs in response to DENV infection, is elevated during severe dengue, is proposed to inhibit interferon, and could potentially recruit target cells to sites of infection. We previously showed that expression of DENV NS5 activates the IL-8 promoter, induces IL-8 transcription ...


The Role Of Adaptor Protein Complex-3 Delta-Mediated Hiv-1 Gag Trafficking In Hiv-1 Replication: A Dissertation, Adonia Lee Kim May 2012

The Role Of Adaptor Protein Complex-3 Delta-Mediated Hiv-1 Gag Trafficking In Hiv-1 Replication: A Dissertation, Adonia Lee Kim

GSBS Dissertations and Theses

The process of HIV-1 particle production is a multi-step process directed by the viral structural protein Gag. As Gag is the only viral protein required to form virus-like particles, it presents a viable target for anti-viral therapeutics of which there are currently none. Although the functions of Gag during the particle assembly process have been well characterized, one of the least known parts of the assembly process is how Gag is targeted to the site of virus assembly.

Two main virus assembly sites have been identified in cells that support HIV-1 replication: the plasma membrane or multivesicular bodies (MVBs). However ...


Hiv-1 R5 Tropism: Determinants, Macrophages, And Dendritic Cells: A Dissertation, Thomas A. Musich May 2012

Hiv-1 R5 Tropism: Determinants, Macrophages, And Dendritic Cells: A Dissertation, Thomas A. Musich

GSBS Dissertations and Theses

Around thirty years ago HIV-1 was identified, and from that point the known epidemic has grown to over 30 million infected individuals. Early on in the course of HIV-1 research, viruses were classified as either syncytia inducing, CXCR4-using, T-cell tropic or non-syncytia inducing, CCR5-using, macrophage tropic. Since that time, several groups have shown that this is an oversimplification. There is a great deal of diversity amongst CCR5-using HIV-1 variants. There remains a great deal to be discovered regarding HIV-1 CCR5-tropism and how this affects other aspects of HIV-1 infection.

The CD4 binding site (CD4bs) on the HIV-1 envelope plays a ...


Gene Therapy For Very Long Chain Acyl-Coa Dehydrogenase Deficiency Using Adeno-Associated Virus Vectors: A Dissertation, Allison M. Keeler Apr 2012

Gene Therapy For Very Long Chain Acyl-Coa Dehydrogenase Deficiency Using Adeno-Associated Virus Vectors: A Dissertation, Allison M. Keeler

GSBS Dissertations and Theses

Very long chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD deficient mice and patients’ clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD deficient mice were treated systemically with 1x10 12 vector genomes of rAAV9-VLCAD. Expression was detected in the liver, heart and muscle. Also substantial expression of VLCAD was noted in the brain, where it was expressed across different sections of the brain and in different cell types with different morphologies. Biochemical correction was observed in vector-treated mice beginning two weeks post-injection, as characterized by a significant ...


The Subtype Specific And Cross-Reactive T Cell Responses To Influenza Viruses In Humans: A Dissertation, Jenny Aurielle B. Babon Apr 2012

The Subtype Specific And Cross-Reactive T Cell Responses To Influenza Viruses In Humans: A Dissertation, Jenny Aurielle B. Babon

GSBS Dissertations and Theses

Human influenza is a contagious respiratory disease resulting in substantial morbidity and mortality worldwide. With the recent cases of avian influenza infections in humans and the heightened concern for an influenza pandemic arising from these infections, it is essential to understand host responses that would confer protective immunity to influenza. The cell-mediated immune responses to influenza virus play an important role during influenza infection.

To analyze the specificity and diversity of memory T-cell responses, we performed a genome-wide screening of T cell epitopes to influenza A virus in healthy adult donors. We identified a total of 83 peptides, 54 of ...


The Role Of Heterologous Immunity In Mediating Natural Resistance To Infection In Human Subjects: A Dissertation, Levi B. Watkin Mar 2012

The Role Of Heterologous Immunity In Mediating Natural Resistance To Infection In Human Subjects: A Dissertation, Levi B. Watkin

GSBS Dissertations and Theses

Heterologous immunity is a mechanism by which immunological memory within an individual, developed in response to a previous infection, plays a role in the immune response to a subsequent unrelated infection. In murine studies, heterologous immunity facilitated by cross-reactive CD8 T-cell responses can mediate either beneficial (protective immunity) or detrimental effects (e.g. enhanced lung and adipose immunopathology and enhanced viral titers) (Selin et al., 1998; Chen et al., 2001; Welsh and Selin, 2002; Nie et al., 2010; Welsh et al., 2010). Protective heterologous immunity results in enhanced clearance of virus during a subsequent infection with an unrelated pathogen. Such ...


A Population-Based Epidemiological Description Of Socio-Demographic Characteristics And Predictors Of Severity Among Hospitalized 2009 H1n1 Influenza Cases In Massachusetts: A Dissertation, Hilary Placzek Feb 2012

A Population-Based Epidemiological Description Of Socio-Demographic Characteristics And Predictors Of Severity Among Hospitalized 2009 H1n1 Influenza Cases In Massachusetts: A Dissertation, Hilary Placzek

GSBS Dissertations and Theses

The spread of pandemic influenza A (2009 H1N1 influenza) virus resulted in a global influenza pandemic in 2009. During the early stages of the pandemic, population surveillance was crucial. However, officials around the world realized that many of our surveillance and reporting systems were not prepared to respond in a coordinated, integrated way, which made informed public health decision-making very difficult. More accurate estimates of the total number of hospitalized 2009 H1N1 influenza cases were required to calculate population-based 2009 H1N1 influenza-associated mortality, morbidity and hospitalization rates. For instance, how many people were hospitalized with 2009 H1N1 influenza in Massachusetts ...


Primary And Secondary Immune Responses During Sequential West Nile Virus And Japanese Encephalitis Virus Infections: A Dissertation, Derek W. Trobaugh Feb 2012

Primary And Secondary Immune Responses During Sequential West Nile Virus And Japanese Encephalitis Virus Infections: A Dissertation, Derek W. Trobaugh

GSBS Dissertations and Theses

Japanese encephalitis virus (JEV) and West Nile virus (WNV) are closely related Flaviviruses that are important arthropod-borne human pathogens. Both of these viruses can cause encephalitis with significant morbidity and mortality after infection. Flaviviruses co-circulate in many areas of the world, which raises the risk for sequential infection between heterologous viruses. Sequential infection between dengue virus serotypes can lead to cross-protection, but in some cases, it leads to a severe outcome, dengue hemorrhagic fever. Previous work in hamsters and non-human primates demonstrated that prior JEV immunity protects against a lethal WNV infection. However, the ability of prior WNV immunity to ...


Control Of Bovine Papillomavirus E2 Function By Acetylation And The Novel E2 Interacting Protein Rint1: A Dissertation, Edward J. Quinlan Jan 2012

Control Of Bovine Papillomavirus E2 Function By Acetylation And The Novel E2 Interacting Protein Rint1: A Dissertation, Edward J. Quinlan

GSBS Dissertations and Theses

Human papillomavirus infection is the cause of more than 99% of cervical cancer cases. The current vaccine is ineffective therapeutically; highlighting the need for continued papillomavirus research. One avenue that could be explored in this regard is the function of the papillomavirus E2 regulatory proteins. HPV E2 represses expression of the viral E6 and E7 oncoproteins. Reintroduction of E2 into cervical carcinoma cells results in growth arrest and cellular senescence. Understanding the mechanism of how E2 regulates the early promoter may be key to developing new therapeutic and prophylactic vaccines. Here, we describe regulation of E2 through acetylation and possibly ...


Role Of Protein Flexibility In Function, Resistance Pathways And Substrate Recognition Specificity In Hiv-1 Protease: A Dissertation, Seema Mittal Aug 2011

Role Of Protein Flexibility In Function, Resistance Pathways And Substrate Recognition Specificity In Hiv-1 Protease: A Dissertation, Seema Mittal

GSBS Dissertations and Theses

In the 30 years since the Center for Disease Control's Morbidity and Mortality Weekly Report published the first mention of what later was determined to be AIDS (Acquired immunodeficiency syndrome) and HIV (Human immunodeficiency virus) recognized as the causative pathogen, much has been done to understand this disease’s pathogenesis, development of drugs and emergence of drug resistance under selective drug therapy. Highly Active Antiretroviral Therapy (HAART), a combination of drugs that includes HIV-1 reverse transcriptase, protease, and more recently, integrase and entry inhibitors, have helped stabilize the HIV prevalence at extraordinarily high levels. Despite the recent stabilization of ...


Structural Studies Of The Anti-Hiv Human Protein Apobec3g Catalytic Domain: A Dissertation, Shivender Shandilya Aug 2011

Structural Studies Of The Anti-Hiv Human Protein Apobec3g Catalytic Domain: A Dissertation, Shivender Shandilya

GSBS Dissertations and Theses

HIV/AIDS is a disease of grave global importance with over 33 million people infected world-wide and nearly 2 million deaths each year. The rapid emergence of drug resistance, due to viral mutation, renders anti-retroviral drug candidates ineffective with alarming speed and regularity. Instead of targeting mutation prone viral proteins, an alternative approach is to target host proteins that interact with viral proteins and are critical for the HIV life-cycle. APOBEC3G is a host anti-HIV restriction factor that can exert tremendous negative pressure by hypermutating the viral genome and has the potential to be a promising candidate for anti-retroviral therapeutic ...


Investigation Of The C-Terminal Helix Of Hiv-1 Matrix: A Region Essential For Multiple Functions In The Viral Life Cycle: A Dissertation, Laura A. Brandano Jul 2011

Investigation Of The C-Terminal Helix Of Hiv-1 Matrix: A Region Essential For Multiple Functions In The Viral Life Cycle: A Dissertation, Laura A. Brandano

GSBS Dissertations and Theses

Since the first cases were reported over thirty years ago, great strides have been made to control disease progression in people living with HIV/AIDS. However, current estimates report that there are about 34 million individuals infected with HIV worldwide. Critical in the ongoing fight against this pandemic is the continuing development of highly active anti-retroviral therapies, ideally those with novel mechanisms of action. Currently, there are no medications approved for use that exploit the HIV-1 MA protein, despite its central role in multiple stages of the virus life cycle.

This thesis sought to examine whether a highly conserved glutamate ...


Regulation Of Humoral Immunity By Pim Kinases: A Dissertation, Kristen N. Willems Jun 2011

Regulation Of Humoral Immunity By Pim Kinases: A Dissertation, Kristen N. Willems

GSBS Dissertations and Theses

Pim (Provirus Integration site for Moloney murine leukemia virus) kinases are a family of three serine/threonine kinases involved in cell cycle, survival and metabolism. These kinases were first identified in malignant cells and are most often associated with their role in cancer. Their role in immunity and lymphocytes is less well known. To date, it has been shown that Pim 1 and/or Pim 2 are important for T lymphocyte survival and activation when the Akt signaling pathway is inhibited by rapamycin. In addition, our laboratory has shown that Pim 2 is critical for BLyS-mediated naive B lymphocyte survival ...


Mechanisms Of Substrate Recognition By Hcv Ns3/4a Protease Provide Insights Into Drug Resistance: A Dissertation, Keith P. Romano May 2011

Mechanisms Of Substrate Recognition By Hcv Ns3/4a Protease Provide Insights Into Drug Resistance: A Dissertation, Keith P. Romano

GSBS Dissertations and Theses

HCV afflicts many millions of people globally, and antiviral therapies are often ineffective and intolerable. The Food and Drug Administration approved the HCV protease inhibitors telaprevir and boceprevir in May 2011, marking an important milestone in anti-HCV research over the past two decades. Nevertheless, severe drug side effects of combination therapy – flu-like symptoms, depression and anemia – limit patient adherence to treatment regimens. The acquisition of resistance challenges the long-term efficacy of antiviral therapies, including protease inhibitors, as suboptimal dosing allows for the selection of drug resistant viral variants. A better understanding of the molecular basis of drug resistance is therefore ...


Molecular And Functional Properties Of Transmitted Hiv-1 Envelope Variants: A Dissertation, Michael G. Kishko Feb 2011

Molecular And Functional Properties Of Transmitted Hiv-1 Envelope Variants: A Dissertation, Michael G. Kishko

GSBS Dissertations and Theses

In 2008 the Nobel Prize in Physiology or Medicine was awarded to the co-discoverers of the Human Immunodeficiency Virus Type 1 (HIV-1), the causative agent of Acquired Immunodeficiency Syndrome (AIDS). This award acknowledged the enormous worldwide impact of the HIV-1/AIDS pandemic and the importance of research aimed at halting its spread. Since the syndrome was first recognized, 25 million people have succumbed to AIDS and over 33 million are currently infected with HIV-1 (www.unaids.org). The most effective strategy for ending the pandemic is the creation of a prophylactic vaccine. Yet, to date, all efforts at HIV-1 vaccine ...


Immunity, Pathogenesis, And Prevention Of Poxvirus Infections: A Dissertation, Mina O. Seedhom Dec 2010

Immunity, Pathogenesis, And Prevention Of Poxvirus Infections: A Dissertation, Mina O. Seedhom

GSBS Dissertations and Theses

Vaccinia virus (VAC) is the prototypical member of the orthopoxvirus genus of the poxvirus family and the virus used for smallpox vaccinations. The following describes the testing of VAC variants designed to have similar immuno-protective profiles with decreased pathogenicity, examines the immune response to VAC after lethal infection in wild type and lupus-prone mice, and describes a method that allows for the enumeration of VAC-specific CD8+ T in naïve and VAC-immune mice.

The first part describes work examining VAC Wyeth (VAC-Wy) variants engineered to be less pathogenic in vivo. VAC-Wy variants included genes that code for three immunomodulatory proteins, an ...


Cd8+ T Cell Serotype-Cross-Reactivity Is A Predominant Feature Of Dengue Virus Infections In Humans: A Dissertation, Heather L. Friberg-Robertson Nov 2010

Cd8+ T Cell Serotype-Cross-Reactivity Is A Predominant Feature Of Dengue Virus Infections In Humans: A Dissertation, Heather L. Friberg-Robertson

GSBS Dissertations and Theses

The four serotypes of dengue virus (DENV 1-4) have a significant and growing impact on global health. Dengue disease encompasses a wide range of clinical symptoms, usually presenting as an uncomplicated febrile illness lasting 5-7 days; however, a small percentage of infections are associated with plasma leakage and bleeding tendency (called dengue hemorrhagic fever, DHF), which can result in shock. Epidemiological studies indicate that severe dengue disease most often occurs during secondary heterotypic DENV infection. Additionally, plasma leakage (the hallmark of DHF) coincides with defervescence and viral clearance, suggesting that severe disease arises from the immune response to infection rather ...


Regulation Of Cellular And Hiv-1 Gene Expression By Positive Transcription Elongation Factor B: A Dissertation, Siobhan O'Brien Oct 2010

Regulation Of Cellular And Hiv-1 Gene Expression By Positive Transcription Elongation Factor B: A Dissertation, Siobhan O'Brien

GSBS Dissertations and Theses


RNA polymerase II-mediated transcription of HIV-1 genes depends on positive transcription elongation factor b (P-TEFb), the complex of cyclin T1 and CDK9. Recent evidence suggests that regulation of transcription by P-TEFb involves chromatin binding and modifying factors. To determine how P-TEFb may connect chromatin remodeling to transcription, we investigated the relationship between P-TEFb and histone H1. We show that P-TEFb interacts with H1 and that H1 phosphorylation in cell culture correlates with P-TEFb activity. Importantly, P-TEFb also directs H1 phosphorylation during Tat transactivation and wild type HIV-1 infection. Our results also show that P-TEFb phosphorylates histone H1.1 at a ...


Dissecting The Role Of Innate Pattern Recognition Receptors And Interferon Regulatory Factor-5 In The Immune Response To Human Metapneumovirus And Other Pathogens: A Dissertation, Zhaozhao Jiang Aug 2010

Dissecting The Role Of Innate Pattern Recognition Receptors And Interferon Regulatory Factor-5 In The Immune Response To Human Metapneumovirus And Other Pathogens: A Dissertation, Zhaozhao Jiang

GSBS Dissertations and Theses

The Innate immune system is the first line of defense against invading microbial pathogens. It is a fast-acting and non-antigen-specific defense system, which employs germline encoded surveillance systems capable of responding to a broad-spectrum of pathogens. The innate immune system involves a variety of immune cells, which express different profiles of surveillance or detection receptors. Upon sensing pathogens, these receptors trigger cell signalling to turn on transcription of inflammatory cytokines, chemokines, anti-microbial peptides and type I Interferons. These effectors have direct effects on the control of pathogen load and also activate the adaptive immune system, which is ultimately required to ...


A Novel Motif In Hiv-1 Nef That Regulates Mip-1Β Chemokine Release In Macrophages: A Dissertation, Lue Dai Jun 2010

A Novel Motif In Hiv-1 Nef That Regulates Mip-1Β Chemokine Release In Macrophages: A Dissertation, Lue Dai

GSBS Dissertations and Theses

Nef is an accessory protein encoded by human and simian immunodeficiency viruses (HIV and SIV), and is critical for viral pathogenicity in vivo.The structure of Nef has been resolved and the major cellular activities of Nef are generally described as down-regulation of cell surface molecules, enhancement of virus infectivity and regulation of cell signaling and activation. Macrophages represent a key target of HIV-1 infection and may contribute significantly to viral pathogenesis by facilitating viral propagation, maintaining a viral reservoir and regulating viral replication. During HIV-1 infection, various cytokines and chemokines are induced for viral advantages more than for host ...


A Tale Of Two Arfs: Tumor Suppressor And Anti-Viral Functions Of P14arf: A Dissertation, Michael W. Straza May 2010

A Tale Of Two Arfs: Tumor Suppressor And Anti-Viral Functions Of P14arf: A Dissertation, Michael W. Straza

GSBS Dissertations and Theses

Animals have evolved complicated and overlapping mechanisms to guard against the development of cancer and infection by pathogenic organisms. ARF, a potent tumor suppressor, positively regulates p53 by antagonizing p53’s negative regulator, MDM2, which in turn results in either apoptosis or cell cycle arrest. ARF also has p53-independent tumor suppressor activity. The CtBP transcriptional co-repressors promote cancer cell survival and migration/invasion. CtBP senses cellular metabolism via a regulatory dehydrogenase domain, and is a target for negative regulation by ARF. ARF targets CtBP to the proteasome for degradation, which results in the up regulation of proapoptotic BH3-only proteins, and ...


Exploring Molecular Mechanisms Of Drug Resistance In Hiv-1 Protease Through Biochemical And Biophysical Studies: A Dissertation, Rajintha M. Bandaranayake May 2010

Exploring Molecular Mechanisms Of Drug Resistance In Hiv-1 Protease Through Biochemical And Biophysical Studies: A Dissertation, Rajintha M. Bandaranayake

GSBS Dissertations and Theses

The human immunodeficiency virus type-1 (HIV-1) is the leading cause of acquired immunodeficiency syndrome (AIDS) in the world. As there is no cure currently available to treat HIV-1 infections or AIDS, the major focus of drug development efforts has been to target viral replication in an effort to slow down the progression of the infection to AIDS. The aspartyl protease of HIV-1 is an important component in the viral replication cycle and thus, has been an important anti-HIV-1 drug target. Currently there are nine protease inhibitors (PIs) that are being used successfully as a part of highly active antiretroviral therapy ...


Regulation Of Immune Pathogenesis By Antigen-Specific Cd8 T Cells Following Sequential Heterologous Infections: A Dissertation, Alex T. Chen Apr 2010

Regulation Of Immune Pathogenesis By Antigen-Specific Cd8 T Cells Following Sequential Heterologous Infections: A Dissertation, Alex T. Chen

GSBS Dissertations and Theses

Previously, our lab demonstrated that heterologous immunity could result in either gain or loss of protective immunity and alteration in immune pathology following infection by a second un-related pathogen. One of the prototypical models to study T cell-mediated heterologous immunity involves two distantly related arenaviruses, namely lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PV). Each virus encodes a cross-reactive CD8 epitope that has six out of eight in amino acid (aa) similarity with respect to its counterpart at the position 205-212 of the nucleoprotein (NP205). Heterologous challenge between LCMV and PV results in 1) expansion of the cross-reactive NP205-specific CD8 ...


Antibody Responses Elicited By Dna Prime-Protein Boost Hiv Vaccines: A Dissertation, Michael Vaine Apr 2010

Antibody Responses Elicited By Dna Prime-Protein Boost Hiv Vaccines: A Dissertation, Michael Vaine

GSBS Dissertations and Theses

The best known correlate of protection provided by vaccines is the presence of pathogen specific antibodies after immunization. However, against the Human Immunodeficiency Virus-1 (HIV-1) the mere presence of antibodies specific for the viral Envelope (Env) protein is not sufficient to provide protection. This necessitates in depth study of the humoral responses elicited during infection and by vaccination. While a significant amount of effort has been invested in studying the evolution of antibody responses to viral infection, only limited progress in understanding antibody responses elicited through vaccination has been made. In the studies described here, I attempt to rectify this ...


Identification And Characterization Of Snapin As A Novel Antagonist Of Hiv-1 Egress: A Dissertation, Patrick Younan Apr 2010

Identification And Characterization Of Snapin As A Novel Antagonist Of Hiv-1 Egress: A Dissertation, Patrick Younan

GSBS Dissertations and Theses

Vpu has been shown to possess two distinct roles in the pathogenesis of HIV. First, Vpu has been shown to down-regulate the expression of CD4 molecules at the plasma membrane of infected cells by targeting CD4 molecules for degradation in the endoplasmic reticulum. Second, Vpu promotes viral egress in specific cell lines termed non-permissive cells by mechanism that remain relatively unclear.

Therefore, experiments were conducted in order to identify cellular factors involved in the Vpu-dependent phenotype. Using full-length Vpu as bait in yeast two-hybrid experiments, several candidate cellular factors were identified. One protein, SNAPIN, was identified as a cellular factor ...