Virology Commons^™

Principles For Enhancing Virus Capsid Capacity And Stability From A Thermophilic Virus Capsid Structure, Nicholas P. Stone, Gabriel Demo, Emily Agnello, Brian A. Kelch

University of Massachusetts Medical School Faculty Publications

The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we used cryoelectron microscopy to determine the capsid structure of the thermostable phage P74-26. We find the P74-26 capsid exhibits an overall architecture that is very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid ...

Alternative Genes For Exploring Ranavirus Phylogenetics: Four Core Genes Compared To The Major Capsid Protein And The Whole Genome., Abigale Garner

Georgia Undergraduate Research Conference (GURC)

The Iridoviridae is a family of virus that infects invertebrates and poikilothermic vertebrates such as amphibians, reptiles, and fish. Ranavirus is one of the five genera within the Iridoviridae. Ranavirus infections have been seen on every continent. The ranaviruses have 26 core genes, but our study focuses on the utility of: an immediate early protein ICP-46 [open reading frame (ORF) 91R in Frog virus 3 (FV3)]; a transcription elongation factor TIIS (ORF 81R in FV3); Evrl/Air family protein (ORF 88R in FV3); and a hypothetical/putative protein of unknown function (ORF 94R in FV3) as alternative genes for phylogenetic ...

Select Gp120 V2 Domain Specific Antibodies Derived From Hiv And Siv Infection And Vaccination Inhibit Gp120 Binding To Alpha4beta7, Sakaorat Lertjuthaporn, Shan Lu, Yang Lou, Shixia Wang, James Arthos

Open Access Articles

The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin alpha4beta7, a gut-homing receptor. Using both cell-surface expressed alpha4beta7 and a soluble alpha4beta7 heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of alpha4beta7 in a cation -sensitive manner and is inhibited ...

Host And Viral Molecular Patterns Relevant To Pathogenicity And Immunity, Alexander Christian Stabell

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Patterns in nature, many going unnoticed, are a defining characteristic of life. In this thesis, I will describe four studies that I have completed during my doctoral work. These will highlight how both host immune system and viral pathogens harness non-random biological patterns to aid in immunity or increase pathogenicity, respectively. Chapter 2 will describe the evolutionary history of a component of the primate innate immune system, Schlafen11, and its involvement in the defense against viruses. I attempt to show that Schlafen11 takes advantage of the pattern of non-optimal codon usage of HIV-1 transcripts in order to inhibit viral replication ...

Grapevine Vein Clearing Virus: Epidemiological Patterns And Construction Of A Clone, Cory Von Keith

MSU Graduate Theses

Grapevine vein clearing virus (GVCV) is a recently discovered virus belonging to the Badnavirus genus. Characteristic to its name, the virus is associated with a disease where symptoms manifest as pronounced vein-clearing, resulting in severe berry deformation and vine decline in susceptible grape varieties. Sustainable production of wine is dependent on healthy plants. The associated disease is mainly found in Midwest vineyards. Attempts were made in this thesis to provide evidence of causality of the virus to the associated disease and to infer the historical path and migration pattern of GVCV. Conclusions and discussions will provide grape producers with the ...

Sodium Pyruvate Alters The Immune Response To Influenza A Virus Infection In Macrophages, Hazzar Abysalamah

MSU Graduate Theses

ABSTRACT

Pyruvate is the end product of glycolysis. It can either be transported into the mitochondria for use in the TCA cycle or be used to regenerate NAD⁺ during fermentation or aerobic glycolysis (also called the Warburg Effect). I recently discovered that addition of sodium pyruvate to the culture medium during infection of macrophages with influenza A virus affects the production of cytokines involved in immune signaling. While infection of macrophages with influenza A virus resulted in high levels of cytokines (IL-6, IL-1β, and TNF-α) in the absence of sodium pyruvate, the addition of sodium pyruvate significantly impaired cytokine production ...

Bacteriophages As Beneficial Regulators Of The Mammalian Microbiome, Joseph W. Francis, Matthew Ingle, Todd Charles Wood

The Proceedings of the International Conference on Creationism

Much of the research on viruses has concentrated on their disease causing ability. The creation model biomatrix theory predicts that viruses play a beneficial role in cells and organisms. In this report we present a new theory which proposes that mammalian phages (bacteriophages), the most abundant organism associated with mammals, guard and regulate growth of the mammalian microbiome. We base this theory on nearly a century of published evidence that demonstrates that phage can insert into the bacterial genome and cover the surface of bacteria. We propose that this “cloaking” of the bacterial cell surface is an elegant mechanism whereby ...

Integrated Regulation Of Class Ii Human Endogenous Retroviruses In A Breast Cancer Cell Line, Yingguang Liu, Tam D. Nguyen

The Proceedings of the International Conference on Creationism

Endogenous retroviruses (ERVs) are still regarded as foreign invaders by most biologists. Because of structural and positional homology of ERVs in human and ape genomes, they have been considered molecular evidences of common ancestry. Using a breast cancer cell line, we analyzed the regulatory features of a group of human endogenous retroviruses (HERV-K), and found that they contain multiple sequence motifs subjecting them to regulation by sex hormones, a stem cell-specific transcription factor (OCT4), and DNA methylation. Mutation of the OCT4 motif abrogates their response to sex hormones, while methylation of a progesterone-response element enhances receptor-binding. We also found that ...

Innate Detection Of Hiv-1 In Myeloid Dendritic Cells, Sean Matthew Mccauley

GSBS Dissertations and Theses

Protective antiviral immune responses require priming of naïve T cells by dendritic cells (DCs) that have matured sufficiently to produce co-stimulatory cell surface molecules and cytokines. Although only low levels of productive HIV-1 infection are detected in ex vivo DCs following HIV-1 challenge, those few cells exhibit innate activation. Experimentally bypassing blocks to entry and replication leads to more efficient transduction of DCs and maturation as indicated by production of interferons and interferon stimulated genes. Furthermore, similar innate activation occurs upon transduction of macrophages or CD4+ T cells. However, the mechanism by which HIV-1 is detected to activate innate immune ...

Investigating The Viral Ecology Of Global Bee Communities With High-Throughput Metagenomics, David A. Galbraith, Zachary L. Fuller, Allyson M. Ray, Axel Brockmann, Maryann Frazier, Mary W. Gikungu, J. Francisco Iturralde Martinez, Karen M. Kapheim, Jeffrey T. Kerby, Sarah D. Kocher, Oleksiy Losyev, Elliud Muli, Harland M. Patch, Cristina Rosa, Joyce M. Sakamoto, Scott Stanley, Anthony D. Vaudo, Christina M. Grozinger

Biology Faculty Publications

Bee viral ecology is a fascinating emerging area of research: viruses exert a range of effects on their hosts, exacerbate the impacts of other environmental stressors, and, importantly, are readily shared across multiple bee species in a community. However, our understanding of bee viral communities is limited, as it is primarily derived from studies of North American and European Apis mellifera populations. Here, we examined viruses in populations of A. mellifera and 11 other bee species from 9 countries, across 5 continents and Oceania. We developed a novel pipeline to rapidly, inexpensively, and robustly screen for bee viruses. This pipeline ...

An Evaluation Of Host Factors As Novel Therapeutic Targets During Influenza Infection Using Rna Technologies, Michael Ryan Haden Thompson

Electronic Theses, Projects, and Dissertations

Influenza A is a single-stranded, multi-segmented, negative sense RNA virus of the family Orthomyxoviridae and is the causative agent of seasonal Influenza. Influenza viruses cause significant impacts on a global scale regarding public health and economics. Annual influenza virus infections in the United States account for over 200,000 hospitalizations, up to 49,000 deaths, and an $87.1 billion economic burden. Influenza A virus has caused several pandemics since the turn of the 20th century. The effects of Influenza on public health and economics, compounded with low efficacy of the annual vaccine and emerging antiviral resistance, brings to light ...

Characterizing The Role Of N Terminus Of Influenza A Nucleoprotein For Location And Viral Rnp Activity, Jared Lin

Electronic Theses, Projects, and Dissertations

The influenza viral ribonucleoprotein complexes (vRNPs) are responsible for viral RNA synthesis. Each vRNP is comprised of one vRNA segment, the viral RNA dependent RNA polymerase complex (RdRP), and multiple copies of nucleoprotein (NP). NP serves as scaffold in formation of vRNPs, but also regulates vRNP activity. The N-terminus of NP contains a nonconventional nuclear localization signal (NLS1) essential for initial vRNP nuclear import, but also interacts with host RNA helicases to enhance viral RNA replication in the nucleus. NP contains at least one additional NLS sequence, with bioinformatics revealing a third NLS in some NP proteins.

Published yeast-two hybrid ...

P38b And Jak-Stat Signaling Protect Against Invertebrate Iridescent Virus 6 Infection In Drosophila, Cara C. West, Neal S. Silverman

Open Access Articles

The fruit fly Drosophila melanogaster is a powerful model system for the study of innate immunity in vector insects as well as mammals. For vector insects, it is particularly important to understand all aspects of their antiviral immune defenses, which could eventually be harnessed to control the transmission of human pathogenic viruses. The immune responses controlling RNA viruses in insects have been extensively studied, but the response to DNA virus infections is poorly characterized. Here, we report that infection of Drosophila with the DNA virus Invertebrate iridescent Virus 6 (IIV-6) triggers JAK-STAT signaling and the robust expression of the Turandots ...

Tat Controls Transcriptional Persistence Of Unintegrated Hiv Genome In Primary Human Macrophages., Beatrix Meltzer, Deemah Dabbagh, Jia Guo, Fatah Kashanchi, Mudit Tyagi, Yuntao Wu

Medicine Faculty Publications

In HIV infected macrophages, a large population of viral genomes persists as the unintegrated form (uDNA) that is transcriptionally active. However, how this transcriptional activity is controlled remains unclear. In this report, we investigated whether Tat, the viral transactivator of transcription, is involved in uDNA transcription. We demonstrate that de novo Tat activity is generated from uDNA, and this uDNA-derived Tat (uTat) transactivates the uDNA LTR. In addition, uTat is required for the transcriptional persistence of uDNA that is assembled into repressive episomal minichromatin. In the absence of uTat, uDNA minichromatin is gradually silenced, but remains highly inducible by HDAC ...

Downregulation Of Microrna Eca-Mir-128 In Seminal Exosomes And Enhanced Expression Of Cxcl16 In The Stallion Reproductive Tract Are Associated With Long-Term Persistence Of Equine Arteritis Virus, Mariano Carossino, Pouya Dini, Theodore S. Kalbfleisch, Alan T. Loynachan, Igor F. Canisso, Kathleen M. Shuck, Peter J. Timoney, R. Frank Cook, Udeni B. R. Balasuriya

Gluck Equine Research Center Faculty Publications

Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of ...

The Involvement Of Epithelial Cells In Arenavirus-Induced Pathogenesis., Nikole Leslie Margaret Warner

Electronic Theses and Dissertations

Mammalian Arenaviruses are a geographically and genetically diverse family of viruses, which is separated into two sub-groups; the Old World (OW) and New World (NW) groups. Of the OW viruses, Lassa virus (LASV), found endemically in Western Africa, is an important human pathogen, causing hundreds of thousands of infections, and several thousand deaths annually. Interestingly, some villages in endemic regions, up to 45% of the population show seropositivity for the virus. It is hypothesized that seropositivity is a result of natural infection through inhalation or ingestion of infectious particles. However, the exact mechanism is still unknown. LASV’s natural reservoir ...

Investigation Into The Causes And Severity Of The 1918 Influenza Pandemic, Alex T. Freedenberg

The Review: A Journal of Undergraduate Student Research

The 1918 Influenza outbreak is regarded as one of the worst pandemics in human history due to its widespread effects across the globe and its high death rate. This death rate was unusual among influenza infections as most strains do not cause the amount of death that is seen in this outbreak, with 20 million dead as a conservative estimate and 100 million by other estimations. This pandemic was not very well contained for a plethora of reasons. Two main reasons are that it came at a time when understanding viral mechanics still escaped medical professionals, and due to the ...

Changes In The Prevalence Of Salmonella Serovars Associated Swine Production And Correlations Of Avian, Bovine And Swine‐Associated Serovars With Human‐Associated Serovars In The United States (1997–2015), Chaohui Yuan, Adam C. Krull, Chong Wang, M. Erdman, P. J. Fedorka-Cray, C. M. Logue, Annette M. O'Connor

Veterinary Diagnostic and Production Animal Medicine Publications

As Salmonella enterica is an important pathogen of food animals, surveillance programmes for S. enterica serovars have existed for many years in the United States. Surveillance programmes serve many purposes, one of which is to evaluate alterations in the prevalence of serovars that may signal changes in the ecology of the target organism. The primary aim of this study was to evaluate changes in the proportion of S. enterica serovars isolated from swine over a near 20‐year observation period (1997–2015) using four longitudinal data sets from different food animal species. The secondary aim was to evaluate correlations between ...

Restoration Of Phage Growth On A Non-Permissive Host By Bypassing Transcription Termination Signals, Millicent Ronkainen

Honors College Capstone Experience/Thesis Projects

RNA polymerase is the central enzyme in all gene expression. The rpoCY75N mutation in the zinc-binding domain of the β’ subunit of E. coli RNA polymerase blocks a unique RNA-based mechanism of transcription antitermination utilized by bacteriophage HK022 and its relatives. Here, we describe the characterization of mutant phage, orc0368, which overcomes the rpoCY75N mutation. The orc0368 genome varies from the wild type phage genome by 4 single base pair mutations. Three of these mutations were not characterized because they occur in intergenic regions but the fourth was chosen for study because of its location between a series ...

Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban

Program in Molecular Medicine Publications and Presentations

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+ memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1 provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune ...