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cytomegalovirus

  • Human Cytomegalovirus Induces the Expression of the AMPKa2 Subunit To Drive Glycolytic Activation and Support Productive Viral Infection
    Cellular Response to Infection | Spotlight
    Human Cytomegalovirus Induces the Expression of the AMPKa2 Subunit To Drive Glycolytic Activation and Support Productive Viral Infection

    Viruses are obligate parasites that depend on the host cell to provide the energy and molecular building blocks to mass produce infectious viral progeny. The processes that govern viral modulation of cellular resources have emerged as critical for successful infection.

    Diana M. Dunn, Irene Rodriguez-Sanchez, Xenia Schafer, Joshua Munger
  • Human Cytomegalovirus-Induced Autophagy Prevents Necroptosis of Infected Monocytes
    Virus-Cell Interactions | Spotlight
    Human Cytomegalovirus-Induced Autophagy Prevents Necroptosis of Infected Monocytes

    Human cytomegalovirus (HCMV) infection is endemic throughout the world, with a seroprevalence of 40 to 100% depending on geographic location. HCMV infection is generally asymptomatic, but can cause severe inflammatory organ diseases in immunocompromised individuals. The broad array of organ diseases caused by HCMV is directly linked to the systematic spread of the virus mediated by monocytes. Monocytes are naturally programmed to...

    Aaron M. Altman, Michael J. Miller, Jamil Mahmud, Nicholas A. Smith, Gary C. Chan
  • Murine Cytomegalovirus M25 Proteins Sequester the Tumor Suppressor Protein p53 in Nuclear Accumulations
    Virus-Cell Interactions
    Murine Cytomegalovirus M25 Proteins Sequester the Tumor Suppressor Protein p53 in Nuclear Accumulations

    Host cells use a number of factors to defend against viral infection. Viruses are, however, in an arms race with their host cells to overcome these defense mechanisms. The tumor suppressor protein p53 is an important sensor of cell stress induced by oncogenic insults or viral infections, which upon activation induces various pathways to ensure the integrity of cells. Viruses have to counteract many functions of p53, but complex DNA...

    Ivana Kutle, Katarzyna M. Szymańska-de Wijs, Boris Bogdanow, Berislav Cuvalo, Lars Steinbrück, Stipan Jonjić, Karen Wagner, Rainer Niedenthal, Matthias Selbach, Lüder Wiebusch, Martina Dezeljin, Martin Messerle
  • Subclinical Cytomegalovirus and Epstein-Barr Virus Shedding Is Associated with Increasing HIV DNA Molecular Diversity in Peripheral Blood during Suppressive Antiretroviral Therapy
    Genetic Diversity and Evolution
    Subclinical Cytomegalovirus and Epstein-Barr Virus Shedding Is Associated with Increasing HIV DNA Molecular Diversity in Peripheral Blood during Suppressive Antiretroviral Therapy

    As part of this study, we evaluated the molecular characteristics of the HIV DNA reservoir over time during antiretroviral treatment (ART) in relation to those of other chronic viral infections (i.e., cytomegalovirus [CMV] and Epstein-Barr virus [EBV]). We demonstrated that the presence of CMV and high-level EBV DNA in peripheral blood cells was associated with changes in HIV DNA molecular diversity. Specifically, HIV DNA molecular...

    Antoine Chaillon, Masato Nakazawa, Stephen A. Rawlings, Genevieve Curtin, Gemma Caballero, Brianna Scott, Christy Anderson, Sara Gianella
  • Protein S-Nitrosylation of Human Cytomegalovirus pp71 Inhibits Its Ability To Limit STING Antiviral Responses
    Cellular Response to Infection | Spotlight
    Protein S-Nitrosylation of Human Cytomegalovirus pp71 Inhibits Its Ability To Limit STING Antiviral Responses

    In order for a pathogen to establish a successful infection, it must undermine the host cell responses inhibitory to the pathogen. As such, herpesviruses encode multiple viral proteins that antagonize each host antiviral response, thereby allowing for efficient viral replication. Human Cytomegalovirus encodes several factors that limit host countermeasures to infection, including pp71. Herein, we identified a previously...

    Masatoshi Nukui, Kathryn L. Roche, Jie Jia, Paul L. Fox, Eain A. Murphy
  • Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt
    Virus-Cell Interactions
    Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt

    Human cytomegalovirus (HCMV) infection is endemic throughout the world regardless of socioeconomic conditions and geographic locations with a seroprevalence reaching up to 100% in some developing countries. Although asymptomatic in healthy individuals, HCMV can cause severe multiorgan disease in immunocompromised or immunonaive patients. HCMV disease is a direct consequence of monocyte-mediated systematic spread of the virus following...

    Jamil Mahmud, Michael J. Miller, Aaron M. Altman, Gary C. Chan
  • Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccine Elicits Antibody Responses with Greater Durability and Breadth than MF59-Adjuvanted gB Protein Immunization
    Vaccines and Antiviral Agents
    Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccine Elicits Antibody Responses with Greater Durability and Breadth than MF59-Adjuvanted gB Protein Immunization

    Human cytomegalovirus (HCMV) is the most common infectious cause of infant birth defects, resulting in permanent neurological disability for one newborn child every hour in the United States. After more than a half century of research and development, we remain without a clinically licensed vaccine or immunotherapeutic to reduce the burden of HCMV-associated disease. In this study, we sought to improve upon the glycoprotein B protein...

    Cody S. Nelson, Jennifer A. Jenks, Norbert Pardi, Matthew Goodwin, Hunter Roark, Whitney Edwards, Jason S. McLellan, Justin Pollara, Drew Weissman, Sallie R. Permar
  • Polymorphisms in Human Cytomegalovirus Glycoprotein O (gO) Exert Epistatic Influences on Cell-Free and Cell-to-Cell Spread and Antibody Neutralization on gH Epitopes
    Genetic Diversity and Evolution
    Polymorphisms in Human Cytomegalovirus Glycoprotein O (gO) Exert Epistatic Influences on Cell-Free and Cell-to-Cell Spread and Antibody Neutralization on gH Epitopes

    Advances in HCMV population genetics have greatly outpaced understanding of the links between genetic diversity and phenotypic variation. Moreover, recombination between genotypes may shuffle variable loci into various combinations with unknown outcomes. UL74(gO) is an important determinant of HCMV infectivity and one of the most diverse loci in the viral genome. By analyzing interstrain heterologous UL74(gO) recombinants, we showed...

    Le Zhang Day, Cora Stegmann, Eric P. Schultz, Jean-Marc Lanchy, Qin Yu, Brent J. Ryckman
  • Open Access
    Evasion of a Human Cytomegalovirus Entry Inhibitor with Potent Cysteine Reactivity Is Concomitant with the Utilization of a Heparan Sulfate Proteoglycan-Independent Route of Entry
    Vaccines and Antiviral Agents
    Evasion of a Human Cytomegalovirus Entry Inhibitor with Potent Cysteine Reactivity Is Concomitant with the Utilization of a Heparan Sulfate Proteoglycan-Independent Route of Entry

    Human cytomegalovirus (HCMV) is major pathogen of nonimmunocompetent individuals that remains in need of new therapeutic options. Here, we identify a potent antiviral compound (4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid [DIDS]), its mechanism of action, and the chemical properties required for its activity. In doing so, the data argue that cysteine-reactive compounds could have the capacity to be developed for anti-HCMV activity....

    M. J. Murray, N. I. Bonilla-Medrano, Q. L. Lee, S. J. Oxenford, R. Angell, D. P. Depledge, M. B. Reeves
  • Human Cytomegalovirus Decreases Major Histocompatibility Complex Class II by Regulating Class II Transactivator Transcript Levels in a Myeloid Cell Line
    Virus-Cell Interactions
    Human Cytomegalovirus Decreases Major Histocompatibility Complex Class II by Regulating Class II Transactivator Transcript Levels in a Myeloid Cell Line

    Human cytomegalovirus (HCMV) is an opportunistic herpesvirus that is asymptomatic for healthy individuals but that can lead to severe pathology in patients with congenital infections and immunosuppressed patients. Thus, it is important to understand the modulation of the immune response by HCMV, which is understudied in the context of endogenous MHC class II regulation. Using Kasumi-3 cells as a myeloid progenitor cell model...

    Praneet K. Sandhu, Nicholas J. Buchkovich

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