Virology Commons^™

Characterization Of The Anti-Viral Activity Of Schlafen13, Jordan Winfield

Open Access Theses & Dissertations

Schlafen13 (Slfn13) is an enzyme that belongs to the Schlafen family whose expression and function is not very well characterized. The N-terminal has a pseudo dimer structure that contains its catalytic site. There is no characterization functionally or structurally of the C-terminal of Slfn13 other than the prediction of a region with helicase activity. The objective of my Thesis was to increase our understanding of the Slfn family of proteins. Currently, Slfn13 is reported to play a role in the differentiation of monocytes and to function as an endoribonuclease that cleaves tRNA and rRNA molecules in a site-dependent sequence-independent manner. …

Investigation Of Influenza B Virus Replication Potential In Swine Primary Respiratory Epithelial Cells And Phylodynamic Analysis Of Equine Influenza A H3n8 Viruses, Sunayana Shyam Jandhyala

Electronic Theses and Dissertations

Influenza viruses are respiratory pathogens that cause significant mortality worldwide. The subtype of influenza A virus currently affecting worldwide equine populations is H3N8, leading to epidemics and transboundary pandemics. The individual gene segments of an isolate named A/equine/Montana/9564-1/2015 were phylogenetically characterized. BLASTn search revealed that the polymerase basic protein 1 (PB1), polymerase acidic (PA), hemagglutinin (HA), nucleoprotein (NP), and matrix (M) segments of this H3N8 isolate shared the highest percentage identity to A/equine/Tennessee/29A/2014 (H3N8) and the polymerase basic protein 2 (PB2), neuraminidase (NA), and non-structural protein (NS) segments to A/equine/Malaysia/M201/2015 (H3N8). Maximum likelihood phylogenetic trees constructed using H3N8 viral genomes …

Biological And Computational Studies Of The Structure And Function Of Pul103, A Human Cytomegalovirus Tegument Protein, Ashley N. Anderson

Wayne State University Dissertations

Human cytomegalovirus (HCMV) is an enveloped, single segment, double-stranded DNA virus. HCMV infection causes disease in immunocompromised (HIV patients, transplant recipients) and immunodeficient (fetuses, neonates) populations. Current treatments are effective but are either limited in use or can lead to organ damage and/or antiviral resistance, and no vaccines are available. Additional antiviral targets are needed. HCMV pUL103 is a potential antiviral target. pUL103 is a conserved herpesvirus protein present in the tegument, layer of proteins and RNA between the envelope and capsid of HCMV virions. pUL103 helps reorganize cellular secretory machinery (Golgi, endosomes) to form the cytoplasmic virion assembly compartment …

Pneumovirus Infections: Understanding Rsv And Hmpv Entry, Replication, And Spread, Jonathan T. Kinder

Theses and Dissertations--Molecular and Cellular Biochemistry

Pneumoviruses including human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are significant causes of respiratory tract infections globally. Children, elderly, and immunocompromised patients are at the greatest risk for developing severe infections, which can have devastating outcomes. Although these viruses are ubiquitous with significant impacts on human health, there are no antivirals or vaccines available. The only FDA approved therapy is a monoclonal antibody for RSV, given prophylactically during the infectious season, and this treatment is only available for high risk infants. The work presented in this thesis aims to increase our understanding of how these viruses enter, replicate, and …

Hiv-1 Subtypes And Drug Resistance Mutations Among Female Sex Workers Varied In Different Cities And Regions Of The Democratic Republic Of Congo, Eun Hee Kwon, Godefroid M. A. Musema, Jessica Boelter, Sydney Townsend, Desire Tshala-Katumbay, Patrick K. Kayembe, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background Complex mosaic structures of HIV-1 were found in the Democratic Republic of Congo (DRC). Currently, there is limited information on the circulating HIV-1 strains, the distribution of these strains and antiretroviral (ART) resistant viruses in different regions of the country, and the HIV-1 strains harbored by the high-risk groups like female sex workers (FSW) reported to be the source of recombinant and ART resistant viruses.

Methods Dried Blood Spots (DBS), collected from 325 infected FSWs in ten cities from 2012 DRC HIV/STI Integrated Biological and Behavioral Surveillance Survey, were tested for HIV-1 genotypes and antiretroviral resistance mutations. Regional segregation …

How The Cervical Microbiota Contributes To Cervical Cancer Risk In Sub-Saharan Africa, Cameron Klein, Crispin Kahesa, Julius Mwalselage, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Particular states of the cervicovaginal microbiota and viral infections are associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better knowledge of the regional cervicovaginal microbiome is required This review establishes current knowledge of HPV, HIV, cervicovaginal infections, and the cervicovaginal microbiota in sub-Saharan Africa. Because …

The Kaposi’S Sarcoma-Associated Herpesvirus (Kshv) Gh/Gl Complex Is The Predominant Neutralizing Antigenic Determinant In Kshv-Infected Individuals, Yasaman Mortazavi, Salum J. Lidenge, Tara Tran, John T. West, Charles Wood, For Yue Tso

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no prophylactic vaccine against the virus is available. In this study, we characterized the antigenic targets of KSHV-specific neutralizing antibodies (nAbs) in asymptomatic KSHV-infected individuals and KS patients with high nAbs titers. We quantified the extent to which various KSHV envelope glycoproteins (gB, ORF28, ORF68, gH, gL, gM, gN and gpK8.1) adsorbed/removed KSHV-specific nAbs from the plasma of infected individuals. Our study revealed that …

Mycoplasma Co-Infection Is Associated With Cervical Cancer Risk, Cameron Klein, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Tanzania faces one of the highest cervical cancer burdens in the world. Recent work has suggested that the bacterial family Mycoplasmataceae is associated with higher levels of human papillomavirus (HPV), human immunodeficiency virus (HIV), and pre-cancerous cervical lesions. Mycoplasmataceae infection in Tanzania is not well understood, especially when considering the differences between sexually transmitted species of Mycoplasmataceae. To establish the prevalence of common Mycoplasmataceae cervical infections and evaluate their relationship with risk factors for cervical cancer, 1160 Tanzanian women responded to an epidemiological questionnaire and were tested for HIV, HPV, cervical lesions, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma spp., and Lactobacillus …

Epstein Barr Virus-Immortalizedｂlymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and …

A Decade In Review: A Systematic Review Of Universal Influenza Vaccines In Clinical Trials During The 2010 Decade, Brigette N. Corder, Brianna L. Bullard, Gregory Poland, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look …

Species D Adenoviruses As Oncolytic Viral Vectors, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup …

Recommendations For Measuring Hiv Reservoir Size In Cure- Directed Clinical Trials., Luis J. Montaner, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Therapeutic strategies are being clinically tested either to eradicate the latent HIV reservoir or to achieve virologic control in the absence of antiretroviral therapy (ART). Attaining this goal will require a consensus on how best to measure the levels of persistently-infected cells with the potential to cause viral rebound upon ART cessation to assess the results of cure-directed strategies in vivo. Current measurements assess different aspects of the HIV provirus and its functionality, and produce divergent results. Here, we provide the collective insight and position from the BEAT-HIV Martin Delaney Collaboratory on which viral measurements to prioritize in HIV cure-directed …

Elucidating The Impact And Mechanism Of Hepatitis C Virus Cell-To-Cell Spread, Karina Durso-Cain

Dissertations

Virus cell-to-cell spread has been implicated in the establishment of persistent infection and has been shown to be involved in the transmission of antiviral resistant mutants. However, relatively little is known about how virus cell-to-cell spread impacts infection or the specific mechanisms by which cell-to-cell spread occurs. as such, this dissertation focused on investigating HCV cell-to-cell spread not only to learn more about this medically important virus, but also to determine the broader impact cell-to-cell spread has on viral infection dynamics, identify the cellular factors involved, and perhaps ultimately provide insight into antiviral strategies that might enhance the barrier to …

Distinct Roles For Carbohydrate And Protein Receptors In Coronavirus Infection, Enya Qing

Dissertations

Coronaviruses (CoVs) are common human and animal pathogens. in humans, four endemic CoV species together account for one third of mild respiratory infections worldwide. More severe and frequently fatal respiratory pathologies are caused by recent CoV outbreaks that resulted from occasional zoonotic spillover from animal CoV reservoirs, namely, SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Because CoVs threaten global health, any chance of relieving CoV's threat on human populations would rely heavily on our understanding of the mechanistic requirements for CoV tropism, whose major determinant is at the level of viral entry. CoVs have evolved to use …

Zika Virus Inactivates Polyamine Catabolism Via Alternative Splicing To Enhance Infection, Marion Lea Graham

Master's Theses

During viral infection, the virus and host must compete for resources inside the cell. One of these resources is polyamines. Polyamines are small, positively charged molecules that are found in all eukaryotic cells. They play a key role in several cellular functions including growth and proliferation, transcription and translation, and membrane stability. Viruses also rely polyamines for productive replication, utilizing them during DNA/RNa polymerization, nucleic acid packaging, and protein synthesis. in response to a virus infecting a host cell, the host cell will begin to regulate polyamine levels as a way to combat the infection. Polyamine levels are regulated by …

Chloroviruses, James L. Van Etten, Irina V. Agarkova, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large dsDNA, plaque-forming viruses that infect certain chlorella-like green algae; the algae are normally mutualistic endosymbionts of protists and metazoans and are often referred to as zoochlorellae. The viruses are ubiquitous in inland aqueous environments throughout the world and occasionally single types reach titers of thousands of plaque-forming units per ml of native water. The viruses are icosahedral in shape with a spike structure located at one of the vertices. They contain an internal membrane that is required for infectivity. The viral genomes are 290 to 370 kb in size, which encode up to 16 tRNAs and 330 …

Characterization Of Immune Evasion Properties Of The Molluscum Contagiosum Virus Mc163 Protein, William De Martini

Seton Hall University Dissertations and Theses (ETDs)

Poxviruses utilize numerous strategies to prevent activation of the host pro-inflammatory transcription factor, NF-κB. For example, the Molluscum Contagiosum Virus (MCV) expresses several immune evasion molecules that either work directly at the level of NF-κB or IKK, the upstream kinase complex required for canonical NF-κB activation. Presumably these strategies allow MCV to evade host innate immune responses and cause persistent infections. In this dissertation I report the identification of a novel MCV inhibitor of NF-κB activation. Ectopic expression of the MC163 protein in HEK 293T cells resulted in a significant decrease in TNFα- induced NF-κB activation as measured by the …

Cyclophilin A Enhances Hiv-1 Reverse Transcription In Human Microglial Cells, Zachary Michael Ingram

Graduate Theses/Dissertations

Parenchymal microglia represent a susceptible cell type to HIV infection and contribute to HIV Associated Neurocognitive Disorders (HAND). Currently, HIV host-protein interactions in microglia are understudied, but relevant to the design of antiviral drugs. HIV replication events rely on host and viral proteins to evade an immune response while improve replication success. Post-fusion the HIV capsid is released into the cytoplasm and begins trafficking towards the nucleus. During transit viral RNA is transcribed to DNA through reverse transcription (RT). In addition, the HIV capsid that protects the reverse transcription complex disassembles in a step termed uncoating. Once the pre-integration complex …

Role Of Topoisomerase Ii Alpha In Dna Topology And T Cell Responses During Chronic Viral Infections, Stella Chinyere Ogbu

Electronic Theses and Dissertations

The clearance of viruses is largely dependent upon the activation of T cells to generate a robust immune response. However, host responses are suppressed during chronic viral infections. In this thesis, we explored the role of Top2α in DNA topology in individuals with chronic HBV, HCV, and HIV infections. We found that Top2α protein expression and activity were low in T cells derived from chronically virus-infected individuals compared to healthy subjects. Using CD4⁺ T cells treated with Top2α inhibitor or poisoner as a model, we demonstrated that Top2α inhibition disrupts the DNA topology, suppresses DNA repair kinase (ATM), and …

Genome-Wide Variation In Potyviruses, Deepti Nigam, Katherine Latourrette, Pedro F.N. Souza, Hernan Garcia Ruiz

Nebraska Center for Virology: Faculty Publications

Potyviruses (family Potyviridae, genus Potyvirus) are the result of an initial radiation event that occurred 6,600 years ago. The genus currently consists of 167 species that infect monocots or dicots, including domesticated and wild plants. Potyviruses are transmitted in a non-persistent way by more than 200 species of aphids. As indicated by their wide host range, worldwide distribution, and diversity of their vectors, potyviruses have an outstanding capacity to adapt to new hosts and environments. However, factors that confer adaptability are poorly understood. Viral RNA-dependent RNA polymerases introduce nucleotide substitutions that generate genetic diversity. We hypothesized that selection imposed by …