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Effects Of Adenovirus Infection On The Localization Of Cellular Protein Pat1b, Emilee Friedman, Kasey A. Karen 2017 Georgia College and State University

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 ...


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 2017 Yale University School of Medicine

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 ...


Phagephisher: A Pipeline For The Discovery Of Covert Viral Sequences In Complex Genomic Datasets, Thomas Hatzopoulos, Siobhan C. Watkins, Catherine Putonti 2017 Loyola University Chicago

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 ...


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 2017 Loyola University Chicago

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 ...


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 2017 Loyola University Chicago

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 ...


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 2017 Loyola University Chicago

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 2017 University of Massachusetts Medical School

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 ...


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 2017 George Washington University

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 ...


Finding Human Proteins That Bind To A Lassa Virus Protein, Maria Alejandra Pardo Ruge, Veronica J. Heintz, Douglas J. LaCount 2017 University of Los Andes, Colombia

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 2017 Purdue University

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 ...


Advances In Developing Therapies To Combat Zika Virus: Current Knowledge And Future Perspectives, Ashok Munjal, Rekha Khandia, Kuldeep Dharma, Swati Sachan, Kumaragurubaran Karthik, Ruchi Tiwari, Yashpal S. Malik, Deepak Kumar, Raj K. Singh, Hafiz M. N. Iqbal, Sunil K. Joshi 2017 Old Dominion University

Advances In Developing Therapies To Combat Zika Virus: Current Knowledge And Future Perspectives, Ashok Munjal, Rekha Khandia, Kuldeep Dharma, Swati Sachan, Kumaragurubaran Karthik, Ruchi Tiwari, Yashpal S. Malik, Deepak Kumar, Raj K. Singh, Hafiz M. N. Iqbal, Sunil K. Joshi

Bioelectrics Publications

Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and ...


Persistence Of Enteric Viruses On Surfaces Under Varying Environmental Conditions, Nicole L. Turnage 2017 University of Arkansas, Fayetteville

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 ...


Differential Disease Susceptibilities In Experimentally Reptarenavirus-Infected Boa Constrictors And Ball Pythons, Mark D. Stenglein, David Sanchez-Migallon Guzman, Valentina E. Garcia, Marylee L. Layton, Laura L. Hoon-Hanks, Scott M. Boback, M. Kevin Keel, Tracy Drazenovich, Michelle G. Hawkins, Joseph L. DeRisi 2017 Dickinson College

Differential Disease Susceptibilities In Experimentally Reptarenavirus-Infected Boa Constrictors And Ball Pythons, Mark D. Stenglein, David Sanchez-Migallon Guzman, Valentina E. Garcia, Marylee L. Layton, Laura L. Hoon-Hanks, Scott M. Boback, M. Kevin Keel, Tracy Drazenovich, Michelle G. Hawkins, Joseph L. Derisi

Faculty and Staff Publications By Year

Inclusion body disease (IBD) is an infectious disease originally described in captive snakes. It has traditionally been diagnosed by the presence of large eosinophilic cytoplasmic inclusions and is associated with neurological, gastrointestinal, and lymphoproliferative disorders. Previously, we identified and established a culture system for a novel lineage of arenaviruses isolated from boa constrictors diagnosed with IBD. Although ample circumstantial evidence suggested that these viruses, now known as reptarenaviruses, cause IBD, there has been no formal demonstration of disease causality since their discovery. We therefore conducted a long-term challenge experiment to test the hypothesis that reptarenaviruses cause IBD. We infected boa ...


Vorinostat Renders The Replication-Competent Latent Reservoir Of Human Immunodeficiency Virus (Hiv) Vulnerable To Clearance By Cd8 T Cells., Julia A Sung, Katherine Sholtis, Jennifer Kirchherr, Joann D Kuruc, Cynthia L Gay, Jeffrey L Nordstrom, Catherine M Bollard, Nancie M Archin, David M Margolis 2017 George Washington University

Vorinostat Renders The Replication-Competent Latent Reservoir Of Human Immunodeficiency Virus (Hiv) Vulnerable To Clearance By Cd8 T Cells., Julia A Sung, Katherine Sholtis, Jennifer Kirchherr, Joann D Kuruc, Cynthia L Gay, Jeffrey L Nordstrom, Catherine M Bollard, Nancie M Archin, David M Margolis

Pediatrics Faculty Publications

Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA). The LCA is a quantitative viral outgrowth assay (QVOA) that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus ...


Developing A Plant Virus-Based Expression System For The Expression Of Vaccines Against Porcine Reproductive And Respiratory Syndrome Virus, Hong Hanh Tran 2017 The University of Western Ontario

Developing A Plant Virus-Based Expression System For The Expression Of Vaccines Against Porcine Reproductive And Respiratory Syndrome Virus, Hong Hanh Tran

Electronic Thesis and Dissertation Repository

Virus-based expression systems have been widely exploited for the production of recombinant proteins in plants during the last three decades. Advances in technology have boosted scale-up manufacturing of plant-made pharmaceuticals to high levels, via the complementation of transient expression and viral vectors. This combination allows proteins of interest to be produced in plants within a matter of days and thus, is well suited for the development of plant-made vaccines or therapeutics against emerging infectious diseases and potential bioterrorism agents. Several plant-based products are currently in varying stages of clinical development. To investigate the viability of virus-based expression systems for plant-made ...


Adenovirus Prime, Env Protein Boost Vaccine Protects Against Neutralization-Resistant Sivsme660 Variants In Rhesus Monkeys, Brandon F. Keele, Wenjun Li, Erica N. Borducchi, Joseph P. Nkolola, Peter Abbink, Bing Chen, Michael S. Seaman, Dan H. Barouch 2017 Frederick National Laboratory for Cancer Research

Adenovirus Prime, Env Protein Boost Vaccine Protects Against Neutralization-Resistant Sivsme660 Variants In Rhesus Monkeys, Brandon F. Keele, Wenjun Li, Erica N. Borducchi, Joseph P. Nkolola, Peter Abbink, Bing Chen, Michael S. Seaman, Dan H. Barouch

Wenjun Li

Previous studies have shown that DNA prime, Ad5 boost vaccines protect against neutralization-sensitive but not neutralization-resistant virus variants within the SIVsmE660 swarm. Here we show that Ad prime, Env protein boost vaccines protect against neutralization-resistant SIVsmE660 variants. We perform two studies in rhesus monkeys with Ad35/Ad26 vectors expressing SIVmac239 Gag/Pol/Env with or without an AS01B-adjuvanted SIVmac32H gp140 protein boost. In a repetitive, low-dose challenge study, we observe robust protection against acquisition of infection by both Ad Alone and Ad/Env vaccines. In a single, high-dose challenge study, only the Ad/Env vaccine affords significant protection against acquisition ...


Dengue Virus Hijacks A Noncanonical Oxidoreductase Function Of A Cellular Oligosaccharyltransferase Complex, David L. Lin, Natalia A. Cherepanova, Leonia Bozzacco, Margaret R. MacDonald, Reid Gilmore, Andrew W. Tai 2017 University of Michigan-Ann Arbor

Dengue Virus Hijacks A Noncanonical Oxidoreductase Function Of A Cellular Oligosaccharyltransferase Complex, David L. Lin, Natalia A. Cherepanova, Leonia Bozzacco, Margaret R. Macdonald, Reid Gilmore, Andrew W. Tai

Open Access Articles

Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen to identify host dependency factors required for DENV propagation and identified the oligosaccharyltransferase (OST) complex as an essential host factor for DENV infection. Mammalian cells express two OSTs containing either STT3A or STT3B. We found that the canonical catalytic function of the OSTs as oligosaccharyltransferases is not necessary for DENV infection, as cells expressing catalytically inactive STT3A or STT3B are able to support DENV propagation. However, the OST subunit MAGT1 ...


Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer 2017 University of Massachusetts Medical School

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a ...


Sulfolobus Spindle-Shaped Virus 1 Growth Kinetics, Setarah Mohammad Nader 2017 Portland State University

Sulfolobus Spindle-Shaped Virus 1 Growth Kinetics, Setarah Mohammad Nader

PSU McNair Scholars Online Journal

Geothermal and hypersaline environments are rich in viral particles, among which spindle-shaped morphologies predominate. Currently, viruses with spindle- or lemon-shaped virions are unique to Archaea and belong to two distinct viral families. The larger of the two families, the Fuselloviridae, encompasses spindle-shaped viruses with very short tails, which infect Sulfolobus solfataricus and close relatives. Sulfolobus spindle-shaped virus 1 (SSV1) is the best-known member of the family and was one of the first hyperthermophilic archaeal viruses to be isolated. However, our knowledge of fuselloviral life cycles and the relationships between these viruses and their hosts is still limited. As a result ...


Genetic Diversity Of Mycobacteriophages And The Unique Abilities Of Cluster K, Shea A. Morris 2017 Georgia College and State University

Genetic Diversity Of Mycobacteriophages And The Unique Abilities Of Cluster K, Shea A. Morris

The Corinthian

Mycobacteriophage are a diverse set of viruses that infect a broad host range of mycobacterium. Genome analysis of this phage group reveals its diversity and provides evidence that they have experienced substantial horizontal gene transfer Collectively they have a large range of host bacteria they can infect, although each viral type may have a limited host range. However, this range is easily expanded and constantly changing in nature by mutation within and between virus types. These phages can lytically destroy their host mycobacteria, and it is this viral ability that have many mycobacteriophage researchers excited about the potential that phage ...


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