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dc.contributor.authorRadoshitzky, Sheli R.
dc.contributor.authorBecker, Michelle M.
dc.contributor.authorChi, Xiaoli
dc.contributor.authorDong, Lian
dc.contributor.authorLongobardi, Lindsay E.
dc.contributor.authorBoltz, Dutch
dc.contributor.authorKuhn, Jens H.
dc.contributor.authorBavari, Sina
dc.contributor.authorDenison, Mark R.
dc.contributor.authorBaric, Ralph S.
dc.contributor.authorHuang, I-Chueh
dc.contributor.authorBailey, Charles
dc.contributor.authorWeyer, Jessica
dc.contributor.authorChiang, Jessica
dc.contributor.authorBrass, Abraham L.
dc.contributor.authorAhmed, Asim Aminsharif
dc.contributor.authorElledge, Stephen J.
dc.contributor.authorChoe, Hyeryun
dc.contributor.authorFarzan, Michael Reynolds
dc.date.accessioned2011-03-04T17:42:56Z
dc.date.issued2011
dc.identifier.citationHuang, I-Chueh, Charles C. Bailey, Jessica L. Weyer, Sheli R. Radoshitzky, Michelle M. Becker, Jessica J. Chiang, Abraham L. Brass, et al. 2011. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathogens 7(1).en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4737682
dc.description.abstractInterferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP1,2) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi://10.1371/journal.ppat.1001258en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017121/pdf/en_US
dash.licenseLAA
dc.subjectvirologyen_US
dc.subjecthost antiviral responsesen_US
dc.subjecthost invasion and cell entryen_US
dc.titleDistinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virusen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorFarzan, Michael Reynolds
dc.date.available2011-03-04T17:42:56Z
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dc.identifier.doi10.1371/journal.ppat.1001258*
dash.authorsorderedfalse
dash.contributor.affiliatedHuang, I-Chueh
dash.contributor.affiliatedBailey, Charles
dash.contributor.affiliatedBrass, Abraham L.
dash.contributor.affiliatedWeyer, Jessica
dash.contributor.affiliatedChoe, Hyeryun
dash.contributor.affiliatedAhmed, Asim
dash.contributor.affiliatedFarzan, Michael
dash.contributor.affiliatedChiang, Jessica
dash.contributor.affiliatedElledge, Stephen


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