• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Coronavirus Publications
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Coronavirus Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Frieman, M.
    Yount, B.
    Page, C.
    Date
    2012
    Journal
    Journal of Virology
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1128/JVI.05957-11
    Abstract
    SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.
    Keyword
    severe acute respiratory syndrome coronavirus
    SARS-CoV
    pathogenesis
    SARS Virus
    Virulence
    Models, Animal
    Mice
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-84856908736&doi=10.1128%2fJVI.05957-11&partnerID=40&md5=b6c7177125d22167d70874b58ddc586f; http://hdl.handle.net/10713/12424
    ae974a485f413a2113503eed53cd6c53
    10.1128/JVI.05957-11
    Scopus Count
    Collections
    UMB Coronavirus Publications

    entitlement

    Related articles

    • A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice.
    • Authors: Roberts A, Deming D, Paddock CD, Cheng A, Yount B, Vogel L, Herman BD, Sheahan T, Heise M, Genrich GL, Zaki SR, Baric R, Subbarao K
    • Issue date: 2007 Jan
    • Severe acute respiratory syndrome coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates.
    • Authors: Regla-Nava JA, Nieto-Torres JL, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C, Castaño-Rodríguez C, Perlman S, Enjuanes L, DeDiego ML
    • Issue date: 2015 Apr
    • Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice.
    • Authors: Rockx B, Sheahan T, Donaldson E, Harkema J, Sims A, Heise M, Pickles R, Cameron M, Kelvin D, Baric R
    • Issue date: 2007 Jul
    • Complete protection against severe acute respiratory syndrome coronavirus-mediated lethal respiratory disease in aged mice by immunization with a mouse-adapted virus lacking E protein.
    • Authors: Fett C, DeDiego ML, Regla-Nava JA, Enjuanes L, Perlman S
    • Issue date: 2013 Jun
    • Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2'-o-methyltransferase activity.
    • Authors: Menachery VD, Yount BL Jr, Josset L, Gralinski LE, Scobey T, Agnihothram S, Katze MG, Baric RS
    • Issue date: 2014 Apr
    DSpace software (copyright © 2002 - 2022)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.