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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 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 ...


Characterizing The Interaction Between Human Adenovirus E1a And The Transcriptional Repressor Bs69, Ali Zhang 2017 The University of Western Ontario

Characterizing The Interaction Between Human Adenovirus E1a And The Transcriptional Repressor Bs69, Ali Zhang

Electronic Thesis and Dissertation Repository

Protein products of the Early Region 1A (E1A) gene in human adenovirus 5 (HAdV-5) are the first viral proteins expressed upon adenovirus infection. E1A disrupts many cellular physiological events by binding to and regulating an impressive number of host factors. Of particular interest is BS69, a repressor of E1A transactivation. Due to the strong interaction observed between E1A and BS69, I hypothesize that these two proteins function together to disrupt gene expression within an infected cell.

Using in silico modelling and a series of yeast two-hybrid assays, I determined that residues 112-119 of HAdV-5 E1A is the minimal interacting region ...


Seroprevalence Of Antibodies Against Kaposi's Sarcoma-Associated Herpesvirus Among Hiv-Negative People In China, Tiejun Zhang, Zhenqiu Liu, Jun Wang, Veenu Minhas, Charles Wood, Gary M. Clifford, Na He, Silvia Franceschi 2017 Fudan University

Seroprevalence Of Antibodies Against Kaposi's Sarcoma-Associated Herpesvirus Among Hiv-Negative People In China, Tiejun Zhang, Zhenqiu Liu, Jun Wang, Veenu Minhas, Charles Wood, Gary M. Clifford, Na He, Silvia Franceschi

Virology Papers

Background: Little information on the prevalence of Kaposi’s sarcoma associated herpesvirus (KSHV) among HIV-negative individuals is available from Asia.

Methods: In the present study, we report findings from a new survey of KSHV in 983 HIV-negative male migrants from Shanghai and their combination with previous similar surveys of 600 female migrants, 600 female sex-workers (FSW), 1336 sexually transmitted infection (STI) clinic male patients, 439 intravenous drug-users (IVDU), and 226 men having sex with men (MSM) from China. KSHV-specific antibodies against latent and lytic antigens were assessed using Sf9 and BC3 monoclonal immunofluorescence assay. Age-adjusted prevalence ratios (PR) and 95 ...


The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann 2017 Washington University in St. Louis

The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann

Arts & Sciences Electronic Theses and Dissertations

The presence of Leishmania RNA virus 1 (LRV1) in parasites of the Leishmania (Viannia) subgenus increases the virulence of the parasite in mouse models of leishmaniasis and is correlated with treatment failure, relapse, and the development of mucocutaneous disease in humans. LRV1 is not shed or infectious; rather, the infection is persistent, and as yet it is unknown how the parasite controls virus levels. Many eukaryotic organisms use RNA interference (RNAi) to limit virus replication, and Leishmania (Viannia) parasites have an active RNAi pathway. To determine whether Leishmania are capable of using RNAi to control LRV1, we sequenced sRNAs from ...


Inhibiting Infectivity Of The Spindle Shaped Virus Using Silver Nanoparticles, Diana S. Demchenko 2017 Portland State University

Inhibiting Infectivity Of The Spindle Shaped Virus Using Silver Nanoparticles, Diana S. Demchenko

Student Research Symposium

Exploring the inhibiting factors of silver nanoparticles could change the way we approach drug-resistant viruses. In previous research, silver nanoparticles have shown to physically block viruses, such as HIV-1, from infecting its host by theoretically binding to surface receptors on the virus. Since there is little research done in this area, we have decided to combine silver nanoparticles with a virus that thrives within an extreme environment: the Spindle Shaped virus. By combining these two factors, we could reveal the biological and chemical properties that block the virus from infecting its host, Sulfolobus. Currently, we have collected data that shows ...


Elucidating The Role Of Interleukin-17a In West Nile Virus Infection, Dhiraj Acharya 2017 University of Southern Mississippi

Elucidating The Role Of Interleukin-17a In West Nile Virus Infection, Dhiraj Acharya

Dissertations

West Nile virus (WNV) is a neurotropic flavivirus of significant public health importance for which no therapeutics and vaccine are currently available. Interleukin-17A (IL-17A) is an inflammatory cytokine that regulates diverse immune functions, while its role is unclear in host’s immune response to WNV. Furthermore, CD8+ T cells are crucial components of immunity and play a vital role in recovery from WNV infection. Here, we report a previously unrecognized function of IL-17A in regulating CD8+ T cell cytotoxicity. We show that WNV induces the expression of IL-17A in both mouse splenocytes and human peripheral blood mononuclear cells cultured in ...


Production Of Antibodies For Specific Detection Of Dengue Virus-2 By Surface Enhanced Raman Spectroscopy, E. Ashley Thompson 2017 The University of Southern Mississippi

Production Of Antibodies For Specific Detection Of Dengue Virus-2 By Surface Enhanced Raman Spectroscopy, E. Ashley Thompson

Honors Theses

Dengue Virus (DENV) is a flavivirus spread by mosquitoes that are endemic in tropic and subtropic climates. It is the causative pathogen of Dengue Fever, Dengue Hemorrhagic Fever, and Dengue Shock Syndrome. Besides mosquito transmission, DENV can also be transmitted through blood transfusion. Due to the high expense and expertise needed to run tests like ELISA and Polymerase Chain Reaction (PCR) based-assays for DENV detection, a rapid, sensitive and cost effective gold nanoparticles mediated surface-enhanced Raman spectroscopy (SERS) assay has been developed as an alternative assay to detect DENV. In this project, I successfully produced a monoclonal antibody that specifically ...


Isolation Of A Mycobacterium Virus With The Infectivity Rate Tested At Various Temperatures, Katie Wegenast 2017 Bellarmine University

Isolation Of A Mycobacterium Virus With The Infectivity Rate Tested At Various Temperatures, Katie Wegenast

Undergraduate Theses

Isolation techniques developed by the HHMI and the SEA-PHAGES program were used to obtain a bacteriophage from a mixture of loamy clay soil. The sample was retrieved from a forest edge in central Kentucky. The isolate produced large lytic plaques on a lawn of the bacterium Mycobacterium smegmatis. The bacteriophage was purified, amplified, and analyzed using restriction digest analysis with visualization by gel electrophoresis. Restriction digest analysis suggests the virus belongs to a group known as “A”. Mycobacteriophages are placed into distinct groups based on DNA sequences comparison. The next step in the procedure will be to document with an ...


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

University of Massachusetts Medical School Faculty Publications

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 ...


Lysine Residues Of Interferon Regulatory Factor 7 Affect The Replication And Transcription Activatormediated Lytic Replication Of Kaposi’S Sarcomaassociated Herpesvirus/Human Herpesvirus 8, Tianzheng Zhang, Ying Wang, Li Zhang, Bin Liu, Jinhui Xie, Charles Wood, Jinzhong Wang 2017 Nankai University

Lysine Residues Of Interferon Regulatory Factor 7 Affect The Replication And Transcription Activatormediated Lytic Replication Of Kaposi’S Sarcomaassociated Herpesvirus/Human Herpesvirus 8, Tianzheng Zhang, Ying Wang, Li Zhang, Bin Liu, Jinhui Xie, Charles Wood, Jinzhong Wang

Virology Papers

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN ...


Detecting, Cloning, And Screening For Suppressors Of Rna Silencing In Maize Chlorotic Mottle Virus And Sugarcane Mosaic Virus, Nicole E. Bacheller 2017 University of Nebraska-Lincoln

Detecting, Cloning, And Screening For Suppressors Of Rna Silencing In Maize Chlorotic Mottle Virus And Sugarcane Mosaic Virus, Nicole E. Bacheller

Theses, Dissertations, and Student Research in Agronomy and Horticulture

Maize lethal necrosis disease (MLND) is one of the most important viral diseases of maize. MLND occurs when Maize chlorotic mottle virus (MCMV) co-infects the same plant with one of several potyviruses, including Sugarcane mosaic virus, Wheat streak mosaic virus or Maize dwarf mosaic virus. Originally prevalent in the Midwest and Peru in the 1970s, the disease was called corn lethal necrosis (CLN) and was controlled through breeding and sanitation. Recently, the disease has re-emerged in East Africa and is rapidly spreading and threatening the food sources of subsistence-farming populations. This re-emergence has raised several questions about the unknown molecular ...


Neurotrophic Factors Ngf, Gdnf And Ntn Selectively Modulate Hsv1 And Hsv2 Lytic Infection And Reactivation In Primary Adult Sensory And Autonomic Neurons, Andy Y. Yanez, Telvin Harrell, Heather J. Sriranganathan, Angela M. Ives, Andrea S. Bertke 2017 Old Dominion University

Neurotrophic Factors Ngf, Gdnf And Ntn Selectively Modulate Hsv1 And Hsv2 Lytic Infection And Reactivation In Primary Adult Sensory And Autonomic Neurons, Andy Y. Yanez, Telvin Harrell, Heather J. Sriranganathan, Angela M. Ives, Andrea S. Bertke

Medical Diagnostics & Translational Sciences Faculty Publications

Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 ...


Characterization Of Functional Domains Of Equine Infectious Anemia Virus Rev Suggests A Bipartite Rna-Binding Domain, Jae-Hyung Lee, Sean C. Murphy, Michael Belshan, Wendy O. Sparks, Yvonne Wannemuehler, Sijun Liu, Thomas J. Hope, Drena Dobbs, Susan Carpenter 2017 Iowa State University, Ames, Iowa

Characterization Of Functional Domains Of Equine Infectious Anemia Virus Rev Suggests A Bipartite Rna-Binding Domain, Jae-Hyung Lee, Sean C. Murphy, Michael Belshan, Wendy O. Sparks, Yvonne Wannemuehler, Sijun Liu, Thomas J. Hope, Drena Dobbs, Susan Carpenter

Drena Dobbs

Equine infectious anemia virus (EIAV) Rev is an essential regulatory protein that facilitates expression of viral mRNAs encoding structural proteins and genomic RNA and regulates alternative splicing of the bicistronic tat/rev mRNA. EIAV Rev is characterized by a high rate of genetic variation in vivo, and changes in Rev genotype and phenotype have been shown to coincide with changes in clinical disease. To better understand how genetic variation alters Rev phenotype, we undertook deletion and mutational analyses to map functional domains and to identify specific motifs that are essential for EIAV Rev activity. All functional domains are contained within ...


Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky 2017 George Washington University

Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Accumulating evidence implicates Zika virus (ZIKV) in pathogenesis of microcephaly in newborns and Guillain-Barré syndrome in adults. However, it remains unclear which viral proteins are responsible for these effects and what are the underlying mechanisms of their pathogenic activity. A recent paper by Drs. Zhao and Gallo, and their colleagues at University of Maryland in Baltimore used fission yeast for genome-wide analysis of ZIKV proteins. They demonstrated cytopathogenic activity for seven ZIKV proteins, anaC, C, prM, M, E, NS2B and NS4A. This activity was shown to be dependent on oxidative stress, and for NS4A they demonstrated involvement of the TOR ...


Reactivation Of Hiv-1 Proviruses In Immune-Compromised Mice Engrafted With Human Voa-Negative Cd4+ T Cells, Zhe Yuan, Guobin Kang, Wuxun Lu, Qingsheng Li 2017 University of Nebraska-Lincoln

Reactivation Of Hiv-1 Proviruses In Immune-Compromised Mice Engrafted With Human Voa-Negative Cd4+ T Cells, Zhe Yuan, Guobin Kang, Wuxun Lu, Qingsheng Li

Virology Papers

Background: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only reactivate a small fraction of intact proviruses.

Methods: To explore the utility of NOD scid gamma (NSG) mice as an in vivo model to reactivate HIV-1 proviruses from VOA-negative CD4+ T cells, resting CD4+ T cells from an HIV-1 latently infected individual were isolated and the human CD4+ T cells corresponding to VOA-positive and VOA-negative CD4+ T cells were engrafted ...


Correlative Light And Electron Microscopy On Mouse Polyomavirus-Infected Fibroblasts, Christina Henderson 2017 University of Colorado, Boulder

Correlative Light And Electron Microscopy On Mouse Polyomavirus-Infected Fibroblasts, Christina Henderson

Undergraduate Honors Theses

Polyomaviruses are small, DNA tumor viruses that can infect multiple species, including humans. In recent years, the number of identified human polyomaviruses (huPyV) has grown. To identify possible therapeutic targets for huPyVs, a better understanding of virus infection at the structural level is needed. Confocal microscopy allows for the visualization of fluorescently-tagged proteins but without seeing the cell’s subcellular structures, functional information can be lost. Electron microscopy provides structural insight but does not always provide biological or biochemical details. Combining these two approaches can relate biological function to structural information about virus replication. Polyomaviruses (PyV) co-opt host proteins that ...


Clinical And Mucosal Immune Correlates Of Hiv-1 Semen Levels In Antiretroviral-Naive Men., Brendan J W Osborne, Angie K Marsh, Sanja Huibner, Kamnoosh Shahabi, Cindy Liu, Tania Contente, Nico J D Nagelkerke, Colin Kovacs, Erika Benko, Lance Price, Kelly S MacDonald, Rupert Kaul 2017 George Washington University

Clinical And Mucosal Immune Correlates Of Hiv-1 Semen Levels In Antiretroviral-Naive Men., Brendan J W Osborne, Angie K Marsh, Sanja Huibner, Kamnoosh Shahabi, Cindy Liu, Tania Contente, Nico J D Nagelkerke, Colin Kovacs, Erika Benko, Lance Price, Kelly S Macdonald, Rupert Kaul

Environmental and Occupational Health Faculty Publications

Background.

This study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men. Methods.

Paired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry. Results.

Semen HIV RNA was detected at 93% of visits, with >50 ...


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