Virology Commons^™

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 ...

Influenza A Virus Genomic Reassortment And Packaging, Graham Devin Williams

Arts & Sciences Electronic Theses and Dissertations

Influenza A viruses (IAV) are a major human and environmental pathogen. IAV successfully infects a diverse host range and adaptation of new viral strains to humans may cause pandemic events with high morbidity and mortality. As a member of the Orthomyxoviridae family, IAV inherently possesses a segmented genome, which enables a process of segment transmission between viruses following cellular co-infection, a process termed reassortment. The high rate of IAV mutation and continued co-circulation of diverse viral strains in divergent host species leads to the persistent prospect for emergence of new IAV with pandemic potential. Therefore, it is of great importance ...

Effects Of Adenovirus Infection On The Localization Of Cellular Protein Pat1b, Emilee Friedman, Kasey A. Karen

Georgia Journal of Science

Adenoviruses are a diverse family of nonenveloped, double-stranded DNA viruses with a variety of vertebrate hosts including humans. Over 50 serotypes of human adenovirus have been identified, and cause a number of illnesses, including conjunctivitis, gastroenteritis, and respiratory infections. The life cycle of adenovirus is divided into immediate early, early, and late phases, with immediate early proteins controlling transcription and the cell cycle, early proteins being largely regulatory, and late proteins being structural. Early proteins such as E4 11k have been demonstrated to relocalize key cellular proteins, including proteins found within mRNA processing bodies (p-bodies). It is hypothesized that E4 ...

Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose

Graduate Theses and Dissertations

Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness to ...

Molecular Evolution Of Dengue Type 2 Virus In Thailand, Rebeca Rico-Hesse, Lisa M. Harrison, Ananda Nisalak, David W. Vaughn, Siripen Kalayanarooj, Sharone Green, Alan L. Rothman, Francis A. Ennis

Sharone Green

Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained ...

Intrinsic And Innate Defenses Of Neurons: Détente With The Herpesviruses, Lynn Enquist, David A. Leib

Open Dartmouth: Faculty Open Access Articles

Neuroinvasive herpesviruses have evolved to efficiently infect and establish latency in neurons. The nervous system has limited capability to regenerate, so immune responses therein are carefully regulated to be nondestructive, with dependence on atypical intrinsic and innate defenses. In this article we review studies of some of these noncanonical defense pathways and how herpesvirus gene products counter them, highlighting the contributions that primary neuronal in vitro models have made to our understanding of this field.

Phagephisher: A Pipeline For The Discovery Of Covert Viral Sequences In Complex Genomic Datasets, Thomas Hatzopoulos, Siobhan C. Watkins, Catherine Putonti

Catherine Putonti

Obtaining meaningful viral information from large sequencing datasets presents unique challenges distinct from prokaryotic and eukaryotic sequencing efforts. The difficulties surrounding this issue can be ascribed in part to the genomic plasticity of viruses themselves as well as the scarcity of existing information in genomic databases. The open-source software PhagePhisher (http://www.putonti-lab.com/phagephisher) has been designed as a simple pipeline to extract relevant information from complex and mixed datasets, and will improve the examination of bacteriophages, viruses, and virally related sequences, in a range of environments. Key aspects of the software include speed and ease of use; PhagePhisher ...

Freshwater Metaviromics And Bacteriophages: A Current Assessment Of The State Of The Art In Relation To Bioinformatic Challenges, Katherine Bruder, Kema Malki, Alexandria Cooper, Emily Sible, Jason W. Shapiro, Siobhan C. Watkins, Catherine Putonti

Catherine Putonti

Advances in bioinformatics and sequencing technologies have allowed for the analysis of complex microbial communities at an unprecedented rate. While much focus is often placed on the cellular members of these communities, viruses play a pivotal role, particularly bacteria-infecting viruses (bacteriophages); phages mediate global biogeochemical processes and drive microbial evolution through bacterial grazing and horizontal gene transfer. Despite their importance and ubiquity in nature, very little is known about the diversity and structure of viral communities. Though the need for culture-based methods for viral identification has been somewhat circumvented through metagenomic techniques, the analysis of metaviromic data is marred with ...

Genomes Of Gardnerella Strains Reveal An Abundance Of Prophages Within The Bladder Microbiome, Kema Malki, Jason W. Shapiro, Travis Kyle Price, Evann Elizabeth Hilt, Krystal Thomas-White, Trina Sircar, Amy B. Rosenfeld, Michael J. Zilliox, Alan J. Wolfe, Catherine Putonti

Catherine Putonti

Bacterial surveys of the vaginal and bladder human microbiota have revealed an abundance of many similar bacterial taxa. As the bladder was once thought to be sterile, the complex interactions between microbes within the bladder have yet to be characterized. To initiate this process, we have begun sequencing isolates, including the clinically relevant genus Gardnerella. Herein, we present the genomic sequences of four Gardnerella strains isolated from the bladders of women with symptoms of urgency urinary incontinence; these are the first Gardnerella genomes produced from this niche. Congruent to genomic characterization of Gardnerella isolates from the reproductive tract, isolates from ...

Bacteriophages Isolated From Lake Michigan Demonstrate Broad Host-Range Across Several Bacterial Phyla, Kema Malki, Alex Kula, Katherine Bruder, Emily Sible, Thomas Hatzopoulos, Stephanie Steidel, Siobhan C. Watkins, Catherine Putonti

Catherine Putonti

BACKGROUND: The study of bacteriophages continues to generate key information about microbial interactions in the environment. Many phenotypic characteristics of bacteriophages cannot be examined by sequencing alone, further highlighting the necessity for isolation and examination of phages from environmental samples. While much of our current knowledge base has been generated by the study of marine phages, freshwater viruses are understudied in comparison. Our group has previously conducted metagenomics-based studies samples collected from Lake Michigan - the data presented in this study relate to four phages that were extracted from the same samples. FINDINGS: Four phages were extracted from Lake Michigan on ...

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang

Program in Bioinformatics and Integrative Biology Publications and Presentations

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as ...

Detection And Epidemic Dynamic Of Tocv And Ccyv With Bemisia Tabaci And Weed In Hainan Of China, Xin Tang, Xiaobin Shi, Deyong Zhang, Fan Li, Fei Yan, Youjun Zhang, Yong Liu, Xuguo Zhou

Entomology Faculty Publications

Background: In recent years, two of the crinivirus, Tomato chlorosis virus (ToCV) and Cucurbit chlorotic yellows virus (CCYV) have gained increasing attention due to their rapid spread and devastating impacts on vegetable production worldwide. Both of these viruses are transmitted by the sweet potato whitefly, Bemisia tabaci (Gennadius), in a semi-persistent manner. Up to now, there is still lack of report in Hainan, the south of China.

Methods: We used observational and experimental methods to explore the prevalence and incidence dynamic of CCYV and ToCV transmitted by whiteflies in Hainan of China.

Results: In 2016, the chlorosis symptom was observed ...

Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel De Mulder, Devi Sengupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Results

We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on ...

Transient Expression Of Zbtb32 In Anti-Viral Cd8+ T Cells Limits The Magnitude Of The Effector Response And The Generation Of Memory, Hyunmu Shin, Varun N. Kapoor, Gwanghun Kim, Peng Li, Hang-Rae Kim, M. Suresh, Susan M. Kaech, E. John Wherry, Liisa K. Selin, Warren J. Leonard, Raymond M. Welsh, Leslie J. Berg

Open Access Articles

Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells. After acute virus infection, CD8+ T cells deficient in ZBTB32 showed enhanced virus-specific CD8+ T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation. The dysregulation of CD8 ...

Identification And Characterization Of An Interferon Stimulated Gene That Restricts Alphavirus Infection And Pathogenesis, Subhajit Poddar

Arts & Sciences Electronic Theses and Dissertations

Viral infection of host cells induces the Type I interferon (IFN) response, which is

characterized by the production of hundreds of IFN-stimulated genes (ISGs). Altogether, these

ISGs function to induce an antiviral state, hindering or blocking various steps of the viral

lifecycle. Many individual ISGs have potent and broad antiviral functions. However elimination

of a single ISG does not completely abrogate protection, suggesting that other ISGs, although

moderate or moderate when considered alone, must work cooperatively to provide optimal

antiviral activity.

In order to identify and characterize novel ISGs, an attenuated strain of the alphavirus

chikungunya (CHIKV-181/25) was tested ...

Expansion Of Microbial Virology By Impetus Of The Reduction Of Viral Dark Matter, Siddharth Ravindran Krishnamurthy

Arts & Sciences Electronic Theses and Dissertations

Modern metagenomic methods have rapidly accelerated the rate of viral discovery. Currently, to discover a novel virus, deep sequencing reads must align to a known reference virus. While alignment is effective at identifying closely related viruses, highly divergent viruses can often share no discernable sequence alignment with known viruses. Therefore, the accurate classification of viral dark matter – metagenomic sequences that originate from viruses but do not align to any reference virus sequences – is one of the major obstacles in not only discovering novel viruses, but also by extension, comprehensively defining the virome. As viral dark matter results fundamentally from a ...

Finding Human Proteins That Bind To A Lassa Virus Protein, Maria Alejandra Pardo Ruge, Veronica J. Heintz, Douglas J. Lacount

The Summer Undergraduate Research Fellowship (SURF) Symposium

Viral hemorrhagic fevers are severe illnesses caused by many different viruses. Lassa Virus is one of these important pathogens in Western Africa, causing hemorrhagic fever and eventually death without early medical treatment. There is no vaccine and there is little information on host-pathogen interactions. Therefore, the interaction between viral proteins and host targets is useful to understand Lassa virus’s lifecycle and pathology, and to develop ways to prevent infection. In this project, we study the nucleoprotein of Lassa virus (NP), which has been reported to have anti-interferon (IFN) activity through elimination of double stranded RNA (dsRNA). These features could ...

Secreted Ns1 Aids In Dengue Virus Entry By Binding Heparan Sulfate, Morgan E. Schafer, Michael Dibiasio-White, Richard J. Kuhn

The Summer Undergraduate Research Fellowship (SURF) Symposium

A large portion of the world’s population lives in an area where they are at risk of contracting Dengue Virus (DENV). While infection with DENV can result in a wide range of clinical manifestations, from flu-like symptoms to hemorrhagic shock, vascular leakage, and even death, no treatments currently exist. Previous studies have shown that higher levels of viral non-structural protein 1 (NS1) in the blood of infected patients correlate with more severe disease. NS1 has been shown to play many roles in the viral lifecycle, but the mechanisms by which NS1 executes these functions are unknown. Preliminary data from ...

Persistence Of Enteric Viruses On Surfaces Under Varying Environmental Conditions, Nicole L. Turnage

Theses and Dissertations

Human enteric viruses such as human norovirus (hNoV) and Aichivirus A (AiV) are common foodborne viruses with hNoVs being identified as the leading causative agent of foodborne illnesses in the U.S. Moreover, hNoVs have been identified as the leading cause of nonbacterial acute gastroenteritis in the U.S. and worldwide. Fomite surface contamination is a major transmission route for enteric viruses. The application of an optimized virus recovery method from fomites is essential for better understanding of virus persistence under varying environmental conditions (EC). This study aimed to optimize a surface sampling method for virus recovery from nonporous food ...

Genetic Divergence Of Influenza A(H3n2) Amino Acid Substitutions Mark The Beginning Of The 2016-2017 Winter Season In Israel, Aharona Glatman-Freedman, Yaron Drori, Sharon Beni, Nehemya Friedman, Rakefet Pando, Hanna Sefty, Ilana Tal, John Mccauley, Galia Rahav, Nathan Keller, Tamy Shohat, Ella Mendelson, Musa Hindiyeh, Michal Mandelboim

NYMC Faculty Publications

BACKGROUND: Influenza vaccine composition is reevaluated each year due to the frequency and accumulation of genetic changes that influenza viruses undergo. The beginning of the 2016-2017 influenza surveillance period in Israel has been marked by the dominance of influenza A(H3N2).

OBJECTIVES: To evaluate the type, subtype, genetic evolution and amino acid substitutions of influenza A(H3N2) viruses detected among community patients with influenza-like illness (ILI) and hospitalized patients with respiratory illness in the first weeks of the 2016-2017 influenza season.

STUDY DESIGN: Respiratory samples from community patients with influenza-like illness and from hospitalized patients underwent identification, subtyping and molecular ...