Distinct Macrophage Subpopulations Regulate Viral Encephalitis But Not Viral Clearance In The Cns,
2010
Old Dominion University
Distinct Macrophage Subpopulations Regulate Viral Encephalitis But Not Viral Clearance In The Cns, Christina D. Steel, Woong-Ki Kim, Larry Sanford, Laurie Wellman, Sandra Burnett, Nico Van Rooijen, Rochard P. Ciavarra
Biological Sciences Faculty Publications
Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS. …
Virus Silicification Under Simulated Hot Spring Conditions,
2010
Portland State University
Virus Silicification Under Simulated Hot Spring Conditions, James R. Laidler, Kenneth M. Stedman
Biology Faculty Publications and Presentations
Silicification of organisms in silica-depositing environments can impact both their ecology and their presence in the fossil record. Although microbes have been silicified under laboratory and environmental conditions, viruses have not. Bacteriophage T4 was successfully silicified under laboratory conditions that closely simulated those found in silica-depositing hot springs. Virus morphology was maintained, and a clear elemental signature of phosphorus was detected by energy-dispersive X-ray spectrophotometry (EDS).
A Study Of The Ebola Virus Glycoprotein: Disruption Of Host Surface Protein Function And Evasion Of Immune Responses,
2010
University of Pennsylvania
A Study Of The Ebola Virus Glycoprotein: Disruption Of Host Surface Protein Function And Evasion Of Immune Responses, Joseph R. Francica
Publicly Accessible Penn Dissertations
The Ebola virus (EBOV) is a member of the family, Filoviridae, and is the etiological agent of Ebola hemorrhagic fever (EHF). This disease causes significant morbidity and mortality in humans and non-human primates, with human fatality rates reaching 90% during outbreaks of the Zaire subtype. Currently, there are no licensed vaccines or antivirals for EBOV and our understanding of viral pathogenesis is limited. Therefore, further studies examining the pathogenic mechanisms of EBOV are necessary to fully understand and effectively treat EHF. The main Ebola virus glycoprotein (GP) is the only viral protein found on the surface of the Ebola virion …
Regulation Of Ccr5 Ise On Primary Cd4+ Lymphocytes By R5x4 Hiv-1,
2010
University of Pennsylvania
Regulation Of Ccr5 Ise On Primary Cd4+ Lymphocytes By R5x4 Hiv-1, Lamorris M. Loftin
Publicly Accessible Penn Dissertations
HIV-1 strains that use CCR5 predominate after transmission and during the asymptomatic period of disease. However, in up to half of infected people, variants that use CXCR4 emerge, coincident with accelerated disease progression. The earliest CXCR4 using strains to appear, called R5X4 viruses, usually retain CCR5 use. Prototype R5X4 HIV-1 isolates infect macrophages using CCR5 and CXCR4, but CD4+ lymphocyte infection by these viruses is mediated predominantly by CXCR4. Here, we sought to identify obstacles to CCR5 use on CD4+ lymphocytes by R5X4 HIV-1. Using a panel of R5X4 Envs we found that, although CXCR4 was the predominant coreceptor used …
The Role Of The Unfolded Protein Response Regulator Bip In Hcmv Virion Assembly And Egress,
2010
University of Pennsylvania
The Role Of The Unfolded Protein Response Regulator Bip In Hcmv Virion Assembly And Egress, Nicholas J. Buchkovich
Publicly Accessible Penn Dissertations
Human cytomegalovirus (HCMV) regulates the unfolded protein response, including specifically inducing the ER chaperone BiP. The increase in BiP protein during infection is the result of promoter activation by the HCMV MIEPs and La autoantigen activation of the internal ribosome entry site of BiP mRNA. To determine the effects of BiP on HCMV replication, BiP was depleted using the SubAB subtilase cytotoxin or short hairpin RNAs. Depletion of BiP had little effect on viral protein synthesis. However, progeny virion formation was significantly inhibited, suggesting that BiP is important for virion formation. Electron microscopic analysis showed that infected cells were resistant …
Primary Human Mammary Epithelial Cells Endocytose Hiv-1 And Facilitate Viral Infection Of Cd4+ T Lymphocytes,
2010
Dartmouth College
Primary Human Mammary Epithelial Cells Endocytose Hiv-1 And Facilitate Viral Infection Of Cd4+ T Lymphocytes, Stephanie M. Dorosko, Ruth I. Connor
Dartmouth Scholarship
The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4(+) cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4(+) cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4(+) target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription …
Mononucleosis And Antigen-Driven T Cell Responses Have Different Requirements For Interleukin-2 Signaling In Murine Gammaherpesvirus Infection,
2010
Dartmouth College
Mononucleosis And Antigen-Driven T Cell Responses Have Different Requirements For Interleukin-2 Signaling In Murine Gammaherpesvirus Infection, Michael Molloy, Weijun Zhang, Edward Usherwood
Dartmouth Scholarship
Interleukin-2 (IL-2) has been implicated as being necessary for the optimal formation of primary CD8+ T cell responses against various pathogens. Here we have examined the role that IL-2 signaling plays in several aspects of a CD8+ T cell response against murine gammaherpesvirus 68 (MHV-68). Exposure to MHV-68 causes a persistent infection, along with infectious mononucleosis, providing a model for studying these processes in mice. Our study indicates that CD25 is necessary for optimal expansion of the antigen-specific CD8+ T cell response but not for the long-term memory response. Contrastingly, IL-2 signaling through CD25 is absolutely required …
The Glycoproteins Of Porcine Reproductive And Respiratory Syndrome Virus And Their Role In Infection And Immunity,
2010
University of Nebraska-Lincoln
The Glycoproteins Of Porcine Reproductive And Respiratory Syndrome Virus And Their Role In Infection And Immunity, Phani B. Das
Dissertations & Theses in Veterinary and Biomedical Science
The porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen of swine and is known to cause abortion and infertility in pregnant sows and respiratory distress in piglets. PRRSV contains a major glycoprotein (GP5) and three minor glycoproteins (GP2a, GP3, and GP4) on the virion envelope, all of which are required for infectious virus production. To study their interactions amongst each other and with a cellular receptor for PRRSV, CD163, I cloned each of the viral glycoproteins and CD163 in various expression vectors. My studies have shown that while the GP2a, GP3, and GP4 are co-translationally glycosylated, …
5’-Proximal Cis-Acting Rna Signals For Coronavirus Genome Replication,
2010
Microbiology
5’-Proximal Cis-Acting Rna Signals For Coronavirus Genome Replication, Bo-Jhih Guan
Doctoral Dissertations
RNA sequences and higher-order structures in the 5’ and 3’ untranslated regions (UTRs) of positive-strand RNA viruses are known to function as cis-acting elements for translation, replication, and transcription. In coronaviruses, these are best characterized in the group 2a bovine coronavirus (BCoV) and mouse hepatitis virus (MHV), yet their precise mechanistic features are largely undefined. Here, we use a reverse genetics system in MHV to exploit the ~30% nt sequence divergence between BCoV and MHV to establish structure/function relationships of 5’ UTR cis-replication elements. It had been previously shown that a precise replacement of the 391-nt MHV 3’ UTR with …
Hiv Can Establish Latency By Direct Infection Of Resting Cd4+ T Cells,
2010
University of Pennsylvania
Hiv Can Establish Latency By Direct Infection Of Resting Cd4+ T Cells, Luis M. Agosto
Publicly Accessible Penn Dissertations
HIV establishes a latent reservoir in a small pool of resting CD4+ T cells early in the infection of a new host. This viral reservoir has a very slow rate of decay and it is resistant to anti-retroviral therapy and the immune surveillance. This reservoir poses a significant obstacle to the eradication of virus in an infected individual. It is thus of importance to understand how this reservoir is established and what are the requirements for its establishment. One widely accepted theory suggests that latently infected resting cells arise as activated cells become infected during the transition to a resting …
Lentiviral Integration Site Targeting: Host Determinants And Consequences,
2010
University of Pennsylvania
Lentiviral Integration Site Targeting: Host Determinants And Consequences, Keshet Ronen
Publicly Accessible Penn Dissertations
A necessary step in the retroviral lifecycle is integration, the covalent insertion of the viral cDNA into the genome of the infected cell. This means that retroviruses, for example HIV, establish life-long infection. It also means that retroviruses are used as gene-delivery vectors to treat genetic diseases. Integration events are distributed non-randomly in the genome of the infected cell, with characteristic genus-specific preferences. In this dissertation, we focus on the lentiviral class of retroviruses, and explore two aspects of their integration: the means by which integration is targeted to its favored sites, and the consequences of integration at these sites …
Receptor Utilization And Antiviral Cd8 T Cell Responses During Central Nervous System Infection With A Murine Coronavirus,
2010
University of Pennsylvania
Receptor Utilization And Antiviral Cd8 T Cell Responses During Central Nervous System Infection With A Murine Coronavirus, Susan J. Bender
Publicly Accessible Penn Dissertations
Murine coronavirus (mouse hepatitis virus, MHV) infection of the CNS provides a model system for studying viral and host factors affecting pathogenic outcome. CNS infection with the highly neurovirulent rJHM.SD is characterized by extensive viral antigen distribution throughout the brain and few antiviral CD8 T cells at the site of infection, and infected mice succumb to disease by approximately seven days post-infection. In contrast, the less neurovirulent rA59 strain establishes acute infection in the CNS and liver; a robust antiviral CD8 T cell response peaks in the brain at day seven post-infection and coincides with clearance of infectious virus. Mice …
Winter Ecology Of Buggy Creek Virus (Togaviridae, Alphavirus) In The Central Great Plains,
2010
University of Tulsa
Winter Ecology Of Buggy Creek Virus (Togaviridae, Alphavirus) In The Central Great Plains, Charles R. Brown, Stephanie A. Strickler, Amy T. Moore, Sarah A. Knutie, Abinash Padhi, Mary Bomberger Brown, Ginger R. Young, Valerie A. O'Brien, Jerome E. Foster, Nicholas Komar
Papers in Natural Resources
A largely unanswered question in the study of arboviruses is the extent to which virus can overwinter in adult vectors during the cold winter months and resume the transmission cycle in summer. Buggy Creek virus (BCRV; Togaviridae, Alphavirus) is an unusual arbovirus that is vectored primarily by the swallow bug (Hemiptera: Cimicidae: Oeciacus vicarius) and amplified by the ectoparasitic bug’s main avian hosts, the migratory cliff swallow (Petrochelidon pyrrhonota) and resident house sparrow (Passer domesticus). Bugs are sedentary and overwinter in the swallows’ mud nests. We evaluated the prevalence of BCRV and extent of …
Cellular Immunity In Mouse Models Of Viral Encephalitis,
2010
Old Dominion University
Cellular Immunity In Mouse Models Of Viral Encephalitis, Christina Dawn Steel
Theses and Dissertations in Biomedical Sciences
Evidence is presented herein that intranasal application of vesicular stomatitis virus (VSV) caused acute infection of the murine central nervous system (CNS) with associated morbidity and significant mortality in mice. However, VSV encephalitis was not invariably fatal, suggesting that the CNS contained a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we administered VSV via the intranasal route and then characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia, cells widely believed to represent the major APC population in the CNS. To …
A V3 Loop-Dependent Gp120 Element Disrupted By Cd4 Binding Stabilizes The Human Immunodeficiency Virus Envelope Glycoprotein Trimer,
2010
University of Nebraska-Lincoln
A V3 Loop-Dependent Gp120 Element Disrupted By Cd4 Binding Stabilizes The Human Immunodeficiency Virus Envelope Glycoprotein Trimer, Shi-Hua Xiang, Andrés Finzi, Beatriz Pacheco, Kevin Alexander, Wen Yuan, Carlo Rizzuto, Chih-Chin Huang, Peter D. Kwong, Joseph Sodroski
Virology Papers
Human immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding of gp120 to receptors on the target cell alters the gp120-gp41 relationship and activates the membrane-fusing capacity of gp41. Interaction of gp120 with the primary receptor, CD4, results in the exposure of the gp120 third variable (V3) loop, which contributes to binding the CCR5 or CXCR4 chemokine receptors. We show here that insertions in the V3 stem or polar substitutions in a conserved hydrophobic patch near the V3 tip result in decreased gp120-gp41 association …
Effect Of Dipterinyl Calcium Pentahydrate On Hepatitis B Virus Replication In Transgenic Mice,
2010
Utah State University
Effect Of Dipterinyl Calcium Pentahydrate On Hepatitis B Virus Replication In Transgenic Mice, P Moheno, John D. Morrey, D Fuchs
John D. Morrey
Dipterinyl calcium pentahydrate (DCP) has previously been shown to inhibit MDA-MB-231 human breast cancer xenographs in nude mice in a manner correlated with increases in plasma IL-12 and IL-4 concentrations, and decreases in plasma IL-6 levels. DCP also inhibits indoleamine 2,3-dioxygenase (IDO), an immuno-inhibitory enzyme, in human PBMCs (Peripheral Blood Mononuclear Cells).
Assessing Changes In Vascular Permeability In A Hamster Model Of Viral Hemorrhagic Fever,
2010
Utah State University
Assessing Changes In Vascular Permeability In A Hamster Model Of Viral Hemorrhagic Fever, B B. Gowen, J G. Julander, N R. London, M H. Wong, D Larson, John D. Morrey, D Y. Li, M Bray
John D. Morrey
A number of RNA viruses cause viral hemorrhagic fever (VHF), in which proinflammatory mediators released from infected cells induce increased permeability of the endothelial lining of blood vessels, leading to loss of plasma volume, hypotension, multi-organ failure, shock and death. The optimal treatment of VHF should therefore include both the use of antiviral drugs to inhibit viral replication and measures to prevent or correct changes in vascular function. Although rodent models have been used to evaluate treatments for increased vascular permeability (VP) in bacterial sepsis, such studies have not been performed for VHF.
Development Of A New Tacaribe Arenavirus Infection Model And Its Use To Explore Antiviral Activity Of A Novel Aristeromycin Analog,
2010
Utah State University
Development Of A New Tacaribe Arenavirus Infection Model And Its Use To Explore Antiviral Activity Of A Novel Aristeromycin Analog, B B. Gowen, M H. Wong, D Larson, W Ye, K H. Jung, E J. Sefing, R Skirpstunas, D F. Smee, John D. Morrey, S W. Schneller
John D. Morrey
A growing number of arenaviruses can cause a devastating viral hemorrhagic fever (VHF) syndrome. They pose a public health threat as emerging viruses and because of their potential use as bioterror agents. All of the highly pathogenic New World arenaviruses (NWA) phylogenetically segregate into clade B and require maximum biosafety containment facilities for their study. Tacaribe virus (TCRV) is a nonpathogenic member of clade B that is closely related to the VHF arenaviruses at the amino acid level. Despite this relatedness, TCRV lacks the ability to antagonize the host interferon (IFN) response, which likely contributes to its inability to cause …
Effects Of The Combination Of Favipiravir (T-705) And Oseltamivir On Influenza A Virus Infections In Mice,
2010
Utah State University
Effects Of The Combination Of Favipiravir (T-705) And Oseltamivir On Influenza A Virus Infections In Mice, D F. Smee, B L. Hurst, M H. Wong, K W. Bailey, E B. Tarbet, John D. Morrey, Y Furuta
John D. Morrey
Favipiravir (T-705 [6-fluoro-3-hydroxy-2-pyrazinecarboxamide]) and oseltamivir were combined to treat influenza virus A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), and A/Duck/MN/1525/81 (H5N1) infections. T-705 alone inhibited viruses in cell culture at 1.4 to 4.3 µM. Oseltamivir inhibited these three viruses in cells at 3.7, 0.02, and 0.16 µM and in neuraminidase assays at 0.94, 0.46, and 2.31 nM, respectively. Oral treatments were given twice daily to mice for 5 to 7 days starting, generally, 24 h after infection. Survival resulting from 5 days of oseltamivir treatment (0.1 and 0.3 mg/kg/day) was significantly better in combination with 20 mg/kg of body weight/day of T-705 against …
The Role Of Sumoylation Of Ledgf/P75 In Hiv-1 Infection,
2010
University of Texas at El Paso
The Role Of Sumoylation Of Ledgf/P75 In Hiv-1 Infection, Murilo Tadeu Domingues Bueno
Open Access Theses & Dissertations
The lens epithelium-derived growth factor (LEDGF) proteins p75 and p52 are transcriptional co-activators that protect cells from stresses through modulation of stress and heat shock-related genes. Besides regulating such genes, LEDGF/p75 is also important in the process of HOX gene expression and leukemia transformation driven by the MLL histone methyl transferase complex. By exploiting a similar mechanism of interaction between LEDGF/p75 and MLL, the HIV-1 viral protein Integrase (IN) associates with LEDGF/p75 in order to execute efficient viral DNA integration. This present work has identified that LEDGF proteins are posttranslationally modified by SUMO-1 and -3. SUMOylation was found to target …
