Virology Commons^™

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

Primate Immunodeficiency Virus Vpx And Vpr Counteract Transcriptional Repression Of Proviruses By The Hush Complex, Leonid Yurkovetskiy, Mehmet Hakan Guney, Kyusik Kim, Shih Lin Goh, Sean M. Mccauley, Ann Dauphin, William E. Diehl, Jeremy Luban

University of Massachusetts Medical School Faculty Publications

Drugs that inhibit HIV-1 replication and prevent progression to AIDS do not eliminate HIV-1 proviruses from the chromosomes of long-lived CD4+ memory T cells. To escape eradication by these antiviral drugs, or by the host immune system, HIV-1 exploits poorly defined host factors that silence provirus transcription. These same factors, though, must be overcome by all retroviruses, including HIV-1 and other primate immunodeficiency viruses, in order to activate provirus transcription and produce new virus. Here we show that Vpx and Vpr, proteins from a wide range of primate immunodeficiency viruses, activate provirus transcription in human CD4+ T cells. Provirus activation ...

Hiv Suppresses Cervical Neutrophil Infiltration In Women With Normal Or Abnormal Pap Smears, Mika Caplan, Peter C. Angeletti, Duan Loy, Kandali Samwel, Daniela Gonzalez, Crispin Chisanga, Julius Mwaiselage, Asafu Munema, Brenda Bashekera, Kessy Goodwin, John Dustin Loy, John T. West, Charles Wood

UCARE Research Products

Human immunodeficiency virus (HIV) infection of CD4+ T cells results in a weakened immune system due to decreased white blood cells, particularly multi-lobed neutrophils (neutropenia) and other granulocytes.¹ The purpose of this study was to determine whether a correlation exists between HPV/HIV status and presence of neutrophils. To test this, we used a computer software program (QuPath) to analyze neutrophil infiltration seen in pap smears of both HIV+ and HIV- patients from samples collected in Tanzania from three different sites: Bagamoyo, Chalinze, and Dar es Salaam. The software was used to quantify neutrophils per image based on the ...

Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King

Electronic Thesis and Dissertation Repository

As an obligate intracellular parasite, human adenovirus (HAdV) must utilize host factors for survival and replication. Early during infection, its multifunctional E1A protein interacts with an impressive range of cellular target proteins to exert control over the cellular environment. Through these virus-host interactions, E1A massively reprograms both viral and cellular transcription to activate the other HAdV genes, downregulate the host’s immune response, and induce the cell cycle. Consequently, E1A converts the infected cell into a compliant state more amenable for HAdV replication, resulting from its numerous protein-protein interactions. I sought to examine E1A’s interaction with cellular protein kinase ...

Use Of Elispot Assay To Study Hbs-Specific B Cell Responses In Vaccinated And Hbv Infected Humans, Chen Tian, Yuxin Chen, Yong Liu, Shixia Wang, Yang Li, Guiyang Wang, Juan Xia, Xiang-An Zhao, Rui Huang, Shan Lu, Chao Wu

Open Access Articles

Hepatitis B surface antibody (HBsAb) plays a critical role in protecting against infection of hepatitis B virus (HBV) and were extensively studied in literature. At the same time, the status of hepatitis B surface antigen (HBs)-specific B cells in both vaccinated and HBV infected people received limited attention. In the current study, we adopted a highly specific B-cell Enzyme Linked ImmunoSpot (ELISpot) assay to analyze HBs-specific B cells in various clinical settings: healthy individuals with the history of HBV vaccination before and after receiving an extra HBV vaccine boost, people chronically infected with HBV (CHB) in various clinical stages ...

The Three-Fold Axis Of The Hiv-1 Capsid Lattice Is The Species-Specific Binding Interface For Trim5alpha, Damien Morger, Franziska Zosel, Martin Buhlmann, Sara Zuger, Maximilian Mittelviefhaus, Benjamin Schuler, Jeremy Luban, Markus G. Grutter

Open Access Articles

Rhesus TRIM5alpha (rhTRIM5alpha) potently restricts replication of human immunodeficiency virus type 1 (HIV-1). Restriction is mediated through direct binding of the C-terminal B30.2 domain of TRIM5alpha to the assembled HIV-1 capsid core. This host-pathogen interaction involves multiple capsid molecules within the hexagonal HIV-1 capsid lattice. However, the molecular details of this interaction and the precise site at which the B30.2 domain binds remain largely unknown. The human orthologue of TRIM5alpha (hsTRIM5alpha) fails to block infection by HIV-1 both in vivo and in vitro This is thought to be due to differences in binding to the capsid lattice. To ...

Herpes Icp8 Protein Stimulates Homologous Recombination In Human Cells, Melvys Valledor, Richard S. Myers, Paul C. Schiller

University of Massachusetts Medical School Faculty Publications

Recombineering has transformed functional genomic analysis. Genome modification by recombineering using the phage lambda Red SynExo homologous recombination proteins Beta in Escherichia coli has approached 100% efficiency. While highly efficient in E. coli, recombineering using the Red SynExo in other organisms declines in efficiency roughly correlating with phylogenetic distance from E. coli. SynExo recombinases are common to double-stranded DNA viruses infecting a variety of organisms, including humans. Human Herpes virus Type 1 (HHV1) encodes a SynExo comprised of ICP8 synaptase and UL12 exonuclease. In a previous study, the Herpes SynExo was reconstituted in vitro and shown to catalyze a model ...

On The Demographic And Selective Forces Shaping Patterns Of Human Cytomegalovirus Variation Within Hosts, Andrew M. Sackman, Susanne P. Pfeifer, Timothy F. Kowalik, Jeffrey D. Jensen

Open Access Articles

Human cytomegalovirus (HCMV) is a member of the beta -herpesvirus subfamily within Herpesviridae that is nearly ubiquitous in human populations, and infection generally results only in mild symptoms. However, symptoms can be severe in immunonaive individuals, and transplacental congenital infection of HCMV can result in serious neurological sequelae. Recent work has revealed much about the demographic and selective forces shaping the evolution of congenitally transmitted HCMV both on the level of hosts and within host compartments, providing insight into the dynamics of congenital infection, reinfection, and evolution of HCMV with important implications for the development of effective treatments and vaccines.

A Long Cytoplasmic Loop Governs The Sensitivity Of The Anti-Viral Host Protein Serinc5 To Hiv-1 Nef, Weiwei Dai, Yoshiko Usami, Yuanfei Wu, Heinrich G. Gottlinger

Open Access Articles

We recently identified the multipass transmembrane protein SERINC5 as an antiviral protein that can potently inhibit HIV-1 infectivity and is counteracted by HIV-1 Nef. We now report that the anti-HIV-1 activity, but not the sensitivity to Nef, is conserved among vertebrate SERINC5 proteins. However, a Nef-resistant SERINC5 became Nef sensitive when its intracellular loop 4 (ICL4) was replaced by that of Nef-sensitive human SERINC5. Conversely, human SERINC5 became resistant to Nef when its ICL4 was replaced by that of a Nef-resistant SERINC5. In general, ICL4 regions from SERINCs that exhibited resistance to a given Nef conferred resistance to the same ...