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Comprehensive Computational Assessment And Evaluation Of Epstein Barr Virus (Ebv) Variations, Mirnas, And Ebers In Ebl, Aml And Across Cancers, Mercedeh J. Movassagh Apr 2019

Comprehensive Computational Assessment And Evaluation Of Epstein Barr Virus (Ebv) Variations, Mirnas, And Ebers In Ebl, Aml And Across Cancers, Mercedeh J. Movassagh

GSBS Dissertations and Theses

Viruses are known to be associated with 20% of human cancers. Epstein Barr virus (EBV) in particular is the first virus associated with human cancers. Here, we computationally detect EBV and explore the effects of this virus across cancers by taking advantage of the fact that EBV microRNAs (miRNAs) and Epstein Barr virus small RNAs (EBERs) are expressed at all viral latencies. We identify and characterize two sub-populations of EBV positive tumors: those with high levels of EBV miRNA and EBERS expression and those with medium levels of expression.

Based on principal component analysis (PCA) and hierarchical clustering of viral ...


The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista Oct 2016

The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista

GSBS Dissertations and Theses

While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are poorly defined. Although extensive work has been done to examine the role of antigen (Ag) in shaping memory formation, most studies focus on the requirements during the first few days of the response known as the priming phase. Little is known about whether or not Ag re-encounter by effector T cells (late Ag) alters CD4 memory T cell formation. Since influenza infection produces a large, heterogeneous, protective CD4 memory T cell population, I used this model to examine the role of late ...


Fc Receptor-Mediated Activities Of Env-Specific Monoclonal Antibodies Generated From Human Volunteers Receiving A Dna Prime-Protein Boost Hiv Vaccine: A Dissertation, Matthew R. Costa Oct 2016

Fc Receptor-Mediated Activities Of Env-Specific Monoclonal Antibodies Generated From Human Volunteers Receiving A Dna Prime-Protein Boost Hiv Vaccine: A Dissertation, Matthew R. Costa

GSBS Dissertations and Theses

Human immunodeficiency type 1 (HIV-1) is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’ infection and as a result, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that a moderate protection is possible, which may correlate with antibody dependent cellular cytotoxicity (ADCC) activity. Previous studies in the Lu lab demonstrated that in an HIV-1 vaccine phase I trial, DP6-001, a polyvalent Env DNA prime-protein boost formulation, could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities along with multiple Fc ...


Viral Proteases As Drug Targets And The Mechanisms Of Drug Resistance: A Dissertation, Kuan-Hung Lin Sep 2016

Viral Proteases As Drug Targets And The Mechanisms Of Drug Resistance: A Dissertation, Kuan-Hung Lin

GSBS Dissertations and Theses

Viral proteases have been shown to be effective targets of anti-viral therapies for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). However, under the pressure of therapy including protease inhibitors, the virus evolves to select drug resistance mutations both in the protease and substrates. In my thesis study, I aimed to understand the mechanisms of how this protease−substrate co-evolution contributes to drug resistance. Currently, there are no approved drugs against dengue virus (DENV); I investigated substrate recognition by DENV protease and designed cyclic peptides as inhibitors targeting the prime site of dengue protease.

First, I used X-ray crystallography ...


Tissue Compartmentalization And Tropism Of Hiv-1: A Dissertation, Robin L. Brese Aug 2016

Tissue Compartmentalization And Tropism Of Hiv-1: A Dissertation, Robin L. Brese

GSBS Dissertations and Theses

Despite the development of effective antiretroviral treatments, there is still no cure for HIV-1. Major barriers to HIV-1 eradication include the diversity of intrapatient viral quasispecies and the establishment of reservoirs in tissue sanctuary sites. A better understanding of these populations is required for targeted treatments. While previous studies have examined the relationship between brain and blood or immune tissues, few have looked at and compared the properties of viruses from other tissue compartments. In this study, 75 full length HIV-1 envelopes were isolated from the frontal lobe, occipital lobe, parietal lobe, colon, lung, and lymph node of an HIV-1 ...


Understanding Drug Resistance And Antibody Neutralization Escape In Antivirals: A Dissertation, Kristina L. Prachanronarong Apr 2016

Understanding Drug Resistance And Antibody Neutralization Escape In Antivirals: A Dissertation, Kristina L. Prachanronarong

GSBS Dissertations and Theses

Antiviral drug resistance is a major problem in the treatment of viral infections, including influenza and hepatitis C virus (HCV). Influenza neuraminidase (NA) is a viral sialidase on the surface of the influenza virion and a primary antiviral target in influenza. Two subtypes of NA predominate in humans, N1 and N2, but different patterns of drug resistance have emerged in each subtype. To provide a framework for understanding the structural basis of subtype specific drug resistance mutations in NA, we used molecular dynamics simulations to define dynamic substrate envelopes for NA to determine how different patterns of drug resistance have ...


Hepatitis C Virus: Structural Insights Into Protease Inhibitor Efficacy And Drug Resistance: A Dissertation, Djade I. Soumana Dec 2015

Hepatitis C Virus: Structural Insights Into Protease Inhibitor Efficacy And Drug Resistance: A Dissertation, Djade I. Soumana

GSBS Dissertations and Theses

The Hepatitis C Virus (HCV) is a global health problem as it afflicts an estimated 170 million people worldwide and is the major cause of viral hepatitis, cirrhosis and liver cancer. HCV is a rapidly evolving virus, with 6 major genotypes and multiple subtypes. Over the past 20 years, HCV therapeutic efforts have focused on identifying the best-in-class direct acting antiviral (DAA) targeting crucial components of the viral lifecycle, The NS3/4A protease is responsible for processing the viral polyprotein, a crucial step in viral maturation, and for cleaving host factors involved in activating immunity. Thus targeting the NS3/4A ...


Characterization Of Envelope-Specific Antibody Response Elicited By Hiv-1 Vaccines: A Dissertation, Yuxin Chen Jan 2015

Characterization Of Envelope-Specific Antibody Response Elicited By Hiv-1 Vaccines: A Dissertation, Yuxin Chen

GSBS Dissertations and Theses

Despite 30 years of intensive research,an effective human immunodeficiency virus (HIV) vaccine still remains elusive. The desirable immune response capable of providing protection against HIV acquisition is still not clear. The accumulating evidence learned from a recent vaccine efficacy correlate study not only confirmed the importance of antibody responses, but also highlighted potential protective functions of antibodies with a broad repertoire of HIV-1 epitope specificities and a wide range of different antiviral mechanisms. This necessitates a deep understanding of the complexity and diversity of antibody responses elicited by HIV-1 vaccines. My dissertation characterizes antibody response profiles of HIV-1 Env ...


Modulating Influenza And Heparin Binding Viruses’ Pathogenesis With Extrinsic Receptor Decoy Liposomes: A Dissertation, Gabriel L. Hendricks Jun 2013

Modulating Influenza And Heparin Binding Viruses’ Pathogenesis With Extrinsic Receptor Decoy Liposomes: A Dissertation, Gabriel L. Hendricks

GSBS Dissertations and Theses

Influenza is a severe disease in humans and animals, causing upwards of 40,000 deaths every year in America alone. Influenza A virus (IAV) also causes periodic pandemics every 10 to 50 years, killing millions of people. Despite this, very few effective therapies are available. All strains of IAV are prone to developing resistance to antibodies due to the high mutation rate in the viral genome. Because of this mutation rate, a yearly vaccine must be generated before every flu season, and efficacy varies year to year. IAV has also mutated to escape several of the clinically-approved small molecule inhibitors ...


Adjuvant-Specific Serum Cytokine Profiles In The Context Of A Dna Prime-Protein Boost Hiv-1 Vaccine: A Dissertation, Rachel Buglione-Corbett Apr 2013

Adjuvant-Specific Serum Cytokine Profiles In The Context Of A Dna Prime-Protein Boost Hiv-1 Vaccine: A Dissertation, Rachel Buglione-Corbett

GSBS Dissertations and Theses

In recent years, heterologous prime-boost vaccination constructs have emerged as a promising strategy to generate broad and protective immunity against a variety of pathogens. The utility of DNA vaccination in priming the immune system, in particular, has improved the immunogenicity of vaccines against difficult pathogens such as HIV-1. In addition, many vaccine formulations include an adjuvant to augment immune responses. However, the mechanisms and profiles of many adjuvants remain largely unknown, particularly in the context of such combination immunization approaches.

My thesis research studied the effects of several adjuvants, QS-21, aluminum hydroxide, MPL, and ISCOMATRIX™ adjuvant in the context of ...


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 ...


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 ...


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 ...


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 ...


Telomere Length Dynamics In Human T Cells: A Dissertation, Joel M. O'Bryan Oct 2011

Telomere Length Dynamics In Human T Cells: A Dissertation, Joel M. O'Bryan

GSBS Dissertations and Theses

Telomere length has been shown to be a critical determinant of T cell replicative capacity and in vivo persistence in humans. We evaluated telomere lengths in virus-specific T cells to understand how they may both shape and be changed by the maintenance of memory T cells during a subsequent virus re-infection or reactivation. We used longitudinal peripheral blood samples from healthy donors and samples from a long-term HCV clinical interferon therapy trial to test our hypotheses.

To assess T cell telomere lengths, I developed novel modifications to the flow cytometry fluorescence in situ hybridization (flowFISH) assay. These flowFISH modifications were ...


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 ...


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 ...


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 ...


Maternally Derived Anti-Dengue Antibodies And Risk Of Dhf In Infants: A Case-Control Study, Steven Hatch Aug 2010

Maternally Derived Anti-Dengue Antibodies And Risk Of Dhf In Infants: A Case-Control Study, Steven Hatch

GSBS Dissertations and Theses

This study proposes to directly test the hypothesis that antibody-dependent enhancement (ADE) is the critical factor in the development of dengue hemorrhagic fever (DHF) in infants. DHF occurs in two distinct clinical settings: a) in children and adults with secondary DENV infection, and b) in infants with primary DENV infection born to mothers with prior DENV infection. The ADE hypothesis proposes that pre-existing serotype-cross-reactive non-neutralizing anti-DENV antibodies bind the heterotypic DENV during secondary infection and enhance its uptake into immune cells, leading to increased viral load and DHF. This model suggests that DHF in DENV-infected infants is caused by the ...


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 ...


Description, Classification, And Prediction Of Dengue Illnesses In A Thai Pediatric Cohort: A Dissertation, James A. Potts May 2010

Description, Classification, And Prediction Of Dengue Illnesses In A Thai Pediatric Cohort: A Dissertation, James A. Potts

GSBS Dissertations and Theses

Dengue fever (DF) and dengue hemorrhagic fever (DHF) are emerging infectious diseases which are endemic in many regions of the globe, many of which are resource-poor areas. DHF and DF impose a severe economic health burden in tropical and subtropical areas. Dengue virus causes an acute febrile illness that can be a self-limited febrile illness, as seen in most cases of DF, or a life-threatening illness with plasma leakage and shock, as seen in cases of DHF. A systematic review of the literature revealed gaps in the knowledge base of clinical laboratory findings of dengue illness with regards to longitudinal ...


Energetic And Dynamic Analysis Of Inhibitor Binding To Drug-Resistant Hiv-1 Proteases: A Dissertation, Yufeng Cai Nov 2009

Energetic And Dynamic Analysis Of Inhibitor Binding To Drug-Resistant Hiv-1 Proteases: A Dissertation, Yufeng Cai

GSBS Dissertations and Theses

HIV-1 protease is a very important drug target for AIDS therapy. Nine protease inhibitors have been proved by FDA and used in AIDS treatment. Due to the high replication rate and the lack of fidelity of the HIV-1 reverse transcriptase, HIV-1 virus developed various drug-resistant variants. Although experimental methods such as crystallography and isothermal titration calorimetry provide structural and thermodynamic data on drug-resistant variants, they are unable to discern the mechanism by which the mutations confer resistance to inhibitors. Understanding the drug-resistance mechanism is crucial for developing new inhibitors more tolerant to the drug-resistant mutations. Computational methods such as free ...


Sensitization Of Cd8 T Cells During Acute Viral Infections Impacts Bystander And Latecomer Cd8 T Cell Responses : A Dissertation, Heather D. Marshall Oct 2009

Sensitization Of Cd8 T Cells During Acute Viral Infections Impacts Bystander And Latecomer Cd8 T Cell Responses : A Dissertation, Heather D. Marshall

GSBS Dissertations and Theses

Many virus infections induce a transient state of immune suppression in the infected host. Virus-induced T cell suppression can be caused by T cell activation-induced cell death (AICD), dendritic cell (DC) apoptosis, DC dysfunction, and/or the enhanced expression of immune-suppressive cytokines. It has been previously demonstrated that naïve bystander CD8 T cells derived from hosts experiencing an acute virus-specific T cell response underwent AICD when polyclonally activated by anti-CD3 in vitro (Zarozinski et al., 2000). Susceptibility of naïve bystander T cells to AICD could prevent the development of a new T cell response during an ongoing immune response, and ...


Respiratory Syncytial Virus (Rsv) Induces Innate Immunity Through Toll-Like Receptors And Acquired Immunity Via The Rsv G Protein: A Dissertation, Matthew R. Murawski Jul 2009

Respiratory Syncytial Virus (Rsv) Induces Innate Immunity Through Toll-Like Receptors And Acquired Immunity Via The Rsv G Protein: A Dissertation, Matthew R. Murawski

GSBS Dissertations and Theses

Respiratory syncytial virus (RSV) causes a common infection that is associated with a range of respiratory illnesses from common cold-like symptoms to serious lower respiratory tract illnesses such as pneumonia and bronchiolitis. RSV is the single most important cause of serious lower respiratory tract illness in children < 1 year of age. Host innate and acquired immune responses activated following RSV infection have been suspected as contributing to RSV disease. Toll-like receptors (TLRs) activate innate and acquired immunity and are candidates for playing key roles in the host immune response to RSV. Leukocytes express TLRs including TLR2, TLR6, TLR3, TLR4, and TLR7 that can potentially interact with RSV and promote immune responses following infection. Using knockout mice, we have demonstrated that TLR2 and TLR6 signaling in leukocytes can activate innate immunity against RSV by promoting TNF-α, IL-6, CCL2 (MCP-1), and CCL5 (RANTES) production. As previously noted, TLR4 also contributed to cytokine activation (71, 90). Furthermore, we demonstrated that signals generated following TLR2 and TLR6 activation were important for controlling viral replication in vivo. Additionally, TLR2 interactions with RSV promoted neutrophil migration and dendritic cell activation within the lung. Collectively, these studies indicate that TLR2 is involved in RSV recognition and subsequent innate immune activation and may play a role in modulating acquired immune responses through DCs.

Despite the fact that RSV is the single ...


Toll-Like Receptors: Target Of Hepatitis C Virus: A Dissertation, Serena Soyoung Yunmee Chang Aug 2008

Toll-Like Receptors: Target Of Hepatitis C Virus: A Dissertation, Serena Soyoung Yunmee Chang

GSBS Dissertations and Theses

Hepatitis C Virus (HCV) is the primary cause of liver transplantation due to its chronic nature in up to eighty percent of infected cases. Around 3 percent of the world’s population is infected with HCV. Treatment for HCV is a combined Ribavirin and interferon-α (IFN-α) therapy effective in only fifty to eighty percent of patients depending on HCV genotype. The growing health concern with this disease is the lack of a cure despite liver transplantation. HCV targets hepatocytes, liver cells, but is not cytolytic. HCV has been shown to induce end stage liver disease through sustained inflammation from the ...