Virology Commons^™

T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones

Biomedical Sciences Theses & Dissertations

Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …

Zika Modulates Arthropod Histone Methylation In Mosquito Cells, Telvin Lee Harrell

Biological Sciences Theses & Dissertations

Epigenetics is the heritable series of covalent modifications that affect chromatin structure, gene expression, and protein function. Methylation is one such epigenetic modification that involves the addition of chemical modifying entities, such as methyl groups, on nucleic acids or proteins. Recent studies have reported that Zika virus (ZIKV) modulates methylation of human and viral RNA important for its replication in vertebrate cells. However, little is known whether ZIKV exerts methylation in arthropod vectors. In this study, I show that ZIKV modulates S-adenosyl methionine (SAMe) synthase, an enzyme involved in the production of SAMe, and histone methylation for its survival in …

Molecular Candidates For Blocking The Transmission Of Vector-Borne Diseases, Ashish Naresh Vora

Biological Sciences Theses & Dissertations

Vector-borne diseases (VBDs) require urgent attention as they have a high mortality rate, with 700,000 people dying in a year as of 2017. So far, extremely few reliable vaccination strategies and solutions have emerged. Transmission blocking vaccines are one among many solutions available to manage the control of VBDs. These require identification of both vector and pathogen molecules that play important roles in the transmission, dissemination and establishment of VBDs. Our strategy is to characterize these candidates that play important roles in vector-host-pathogen interactions. This manuscript presents two such studies identifying the participation of two arthropod molecules in vector-host-pathogen interactions. …

Cellular Immunity In Mouse Models Of Viral Encephalitis, Christina Dawn Steel

Theses and Dissertations in Biomedical Sciences

Evidence is presented herein that intranasal application of vesicular stomatitis virus (VSV) caused acute infection of the murine central nervous system (CNS) with associated morbidity and significant mortality in mice. However, VSV encephalitis was not invariably fatal, suggesting that the CNS contained a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we administered VSV via the intranasal route and then characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia, cells widely believed to represent the major APC population in the CNS. To …

The Role Of Human Endogenous Retroviruses In Renal Cell Carcinoma, Michele D. Tisdale

Biological Sciences Theses & Dissertations

Human endogenous retroviruses make up approximately 8-9% of the human genome. A number of expressed HERVs, those that are actively transcribing, have been associated with various cancers. Suppression mechanisms that control HERV expression often fail or become more permissive in tissues where expression should be restricted. Previous studies have identified HERV expression in breast cancer tissues, whereas normal tissue HERV expression remained suppressed. In addition, studies of DNA hypermethylation have correlated with the ability to contribute to cancer development. Hypermethylation of several tumor suppressor genes occurs frequently in cancers and alterations in promoter regions could contribute to the development of …

Interdependent Regulation Of Cytomegalovirus Proteins In Complex, Lisa L. Bolin

Theses and Dissertations in Biomedical Sciences

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes significant morbidity and mortality in the immune compromised. Using the mutine cytomegalovirus (MCMV) model, we identified two genes, M140 and M141, which are determinants of macrophage tropism. Monocytes/macrophages are a critical cell type for cytomegalovirus (CMV) pathogenesis as sites of viral latency and by supporting viral replication and disseminating virus throughout the body. We previously found that the localization of the M140/M141 gene products (pM140/pM141) is different when the proteins are co-expressed as compared to their individual expression. When the proteins are individually expressed pM141 localizes diffusely throughout the cytoplasm and, …

Study Of The Dna Damage Complexes Within The Htlv-1 Tax Oncoprotein Interactome, Sidi Mehdi Belgnaoui

Theses and Dissertations in Biomedical Sciences

Human T-cell leukemia virus type 1 (HTLV-1) is a transforming retrovirus that can give rise to adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax is a virally encoded oncoprotein that is involved in HTLV-1 mediated cellular transformation. It has been hypothesized that Tax induces genomic instability via repression of the cellular DNA damage repair response. Our laboratory has previously shown that the interaction between Tax and various proteins involved in the DNA-damage response pathway impairs the ability of these proteins to mount an efficient repair response. As part of these observations, we proposed that Tax induces …

Comparison Of Immune Correlates, Age Related Changes And Proteomic Profiling Of Healthy Individuals Receiving Influenza Vaccines, Gaurav Basu

Theses and Dissertations in Biomedical Sciences

The burden of influenza related infections is substantial, both in terms of illness, lives lost and economic impact on society. The degree of impact of influenza related infections is much higher in the elderly population where it is a leading cause of catastrophic disability; greatly affecting the quality of life of elderly persons above 65 years of age. Vaccination is the mainstay for control and prevention of influenza infections. There are two vaccine formulations that are licensed for use at present. The inactivated influenza vaccines (TIIV) which have been used for 60 years in all age groups and the new …

Role Of The Human Cytomegalovirus Ie2 Protein On Transcriptional Regulation Of Viral Promoters, Siabhon Michelle Harris

Theses and Dissertations in Biomedical Sciences

Human cytomegalovirus (HCMV) is a ubiquitous pathogen able to cause severe mortality and morbidity in immuno-compromised individuals. Successful infection by HCMV is dependent on expression of viral genes essential for replication. Immediate early (IE) gene products are the first subset of viral genes to be expressed during infection and function as key transcriptional regulators. IE2 is one the most predominantly expressed IE proteins and is essential for HCMV infection. IE2 transactivates several viral promoters, including those of the essential viral DNA polymerase (UL54) and UL112-113 gene regions. IE2 is also able to autoregulate is own expression and repress expression of …

Subcellular Localization Of Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein, Kimberly Anne Fryrear

Theses and Dissertations in Biomedical Sciences

Human T-cell Leukemia Virus Type 1 (HTLV-1) is a transforming retrovirus that gives rise to Adult T-cell Leukemia (ATL) and a variety of other subneoplastic conditions such as HTLV-Associated Myelopathy/Tropical Spastic Paraperesis (HAM/TSP). In ATL, the transformation and immortalization of T-lymphocytes has been attributed to the expression and activity of a single HTLV-1 viral protein, namely the trans-activating protein Tax. Although the exact mechanism of Tax-mediated transformation is uncertain, current studies support a model in which Tax induces genomic instability in the host cell through interference with DNA repair mechanisms, dysregulation of cell cycle progression, transcriptional activation of cellular …

Isolation And Functional Mapping Of Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein Dna-Damage Complexes, Sarah Saionz Durkin

Theses and Dissertations in Biomedical Sciences

Human T-cell Leukemia Virus Type 1 (HTLV-1) is a transforming retrovirus which causes Adult T-cell Leukemia (ATL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Cellular transformation can be caused by a single viral trans-activating protein, Tax. Tax may contribute to transformation through interaction with components of the DNA damage response pathway, promoting cellular genomic instability. We examined cellular Tax complexes in an effort to elucidate potential protein-protein interactions that can model the Tax-induced molecular events.

We also investigated the role of post-translational modification in regulating Tax function. We employed a direct physical analysis of Tax complexes isolated from mammalian …

Interactions Among Murine Cytomegalovirus Us22 Family Gene Products That Influence Viral Pathogenesis, Zaruhi Karabekian

Theses and Dissertations in Biomedical Sciences

Cytomegalovirus (CMV) is a complex, ubiquitous herpesvirus that is characterized by acute, chronic, and latent infections. Monocytes-macrophages are the key target cell type involved in pathogenesis, which is most effectively studied using the murine model of CMV infection. Previously three murine CMV (MCMV) genes (M139, M140, and M141) were identified to regulate viral expression in cultured macrophages and in mice. These genes are members of the US22 gene family with respect to HCMV homology. There is no function assigned to the proteins encoded by these genes. However, deletion of M139, M140, and M141 significantly curtails growth of MCMV in macrophages …

A Study On The Effects Of The N-Terminal Amino Acid Sequence On The Activation Of Human T-Cell Leukemia Virus Type 1 Protease, Hidayah Muhammad Kendall

Chemistry & Biochemistry Theses & Dissertations

Human T-cell leukemia virus type 1 (HTL V-1) is dependent upon the enzymatic activity of its protease for maturation. Maturation of the protease is facilitated by cleavage of specific amino acid residues, followed by dimerization. The effects of the amino acid sequence located N-terminally to the cleavage site on the ability of the protease to become active were the focus of the current study. These amino acid sequences were contributed by the plasmid vector into which the protease gene was inserted.

Surface probability analyses (SPAs) of the vectors, as well as for native sequences which produce the mature protease and …

Structural Characterization Of A Novel Inhibitor Of Hiv Reverse Transcriptase (Hiv Rt), Greggory Jon Woitte

Chemistry & Biochemistry Theses & Dissertations

Human immunodeficiency virus (HIV) infections have become a leading cause of death among young people in the United States today. As the number of HIV infections increases, so too does the cost of treatment. Together, these numbers have prompted an increase in the development of pharmaceutical interventions. HIV reverse transcriptase (HIV RT) has become a suitable target for drug therapy because it is the sole enzyme responsible for HIV replication.

Fucoidan, a sulfated polysaccharide isolated from the brown algae Fucus vesiculosus, has been shown to block a variety of cell adhesion related events including metastasis. In addition, fucoidan has also …

The Kinetic Characterization Of Mutant L289p Of Recombinant Hiv-1 Reverse Transcriptase, Tryn Thomas Stimart

Chemistry & Biochemistry Theses & Dissertations

The Human Immunodeficiency Virus, type 1 (HIV-1) is the causative agent of the Acquired immunodeficiency Syndrome (AIDS). Currently, AIDS is the leading cause of death amongst young people in the United States. The large increase of HIV-1 infections over the past decade has spawned considerable research in fighting the spread of this disease. One area of intense HIV-1 research has focused on the enzyme Reverse Transcriptase (RT) which is an essential enzyme involved in the replication and life cycle of HIV-1. HIV-1 RT is composed of p66 and p51 subunits and is only active as a heterodimer in vivo. …

Characterization Of An Antiviral Agent Based On Nonionic Surfactants And It's Effects On Human Dermal Fibroblasts, Ji Young Li

Biological Sciences Theses & Dissertations

The AIDS ·pandemic has directed various research endeavors towards finding an appropriate method for eliminating all potentially infectious material within bone allografts before implantation into a recipient. To that effect, Panavirocide was conceived by Medicine and Applied Science·s, Inc. This compound, in which three nonionic surfactants serve as the active agents, has been shown to inactivate HIV-1 particles within blood and blood products. Because Panavirocide has never been used with allografts, the purpose of the present research was to characterize the nonionic surfactants for the putative alteration of the formulation by determining the critical micelle concentration values and to determine …

Kinetic Characterization Of A Recombinant C-Terminal Mutant Of Reverse Transcriptase From The Human Immunodeficiency Virus, Thomas S. Heard

Chemistry & Biochemistry Theses & Dissertations

The human immunodeficiency virus (HIV) reverse transcriptase (RT) (EC 2.7.7.49) is the central replication enzyme for HIV. In general, the kinetic mechanism for this and all other polymerases involves the ordered binding of two substrates: a primer-template (PT) followed by a deoxyribonucleoside triphosphate (dNTP). Previous investigations prompted this research when it was discovered that the substrate dNTP, in absence of PT, could protect a recombinant c-terminal mutant HIV-1 RT from inhibition by pyridoxal-5'-monophosphate (PLP), an active-site dNTP inhibitor. In contrast, the non-mutant recombinant HIV-1 RT required both substrates for protection from PLP inhibition. This investigation sought to determine if this …

Isolation And Enumeration Of Enteric Viruses From Primary Wastewater Sludge, Michael Wayne Nath

Biological Sciences Theses & Dissertations

The presence of large numbers of enteric viruses in wastewaters has resulted in concern regarding their significance and consequences for humans. Assessments of relative significance or consequences may most accurately be made following precise measurements of the range of virus types and amounts in wastewaters and sludges and after epidemiological considerations. In this study, results are presented pertaining to enteric virus isolation, concentration, and enumeration from primary wastewater sludges.

As an integral part of a comparison of isolation procedures, several anionic surfactants were examined for extraction of enteric viruses from primary wastewater sludges. Plaquing efficiencies for poliovirus type 2 and …