Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus

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Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus

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dc.contributor.author Radoshitzky, Sheli R.
dc.contributor.author Becker, Michelle M.
dc.contributor.author Chi, Xiaoli
dc.contributor.author Dong, Lian
dc.contributor.author Longobardi, Lindsay E.
dc.contributor.author Boltz, Dutch
dc.contributor.author Kuhn, Jens H.
dc.contributor.author Bavari, Sina
dc.contributor.author Denison, Mark R.
dc.contributor.author Baric, Ralph S.
dc.contributor.author Huang, I-Chueh
dc.contributor.author Bailey, Charles
dc.contributor.author Weyer, Jessica
dc.contributor.author Chiang, Jessica
dc.contributor.author Brass, Abraham L.
dc.contributor.author Ahmed, Asim Aminsharif
dc.contributor.author Elledge, Stephen J.
dc.contributor.author Choe, Hyeryun
dc.contributor.author Farzan, Michael Reynolds
dc.date.accessioned 2011-03-04T17:42:56Z
dc.date.issued 2011
dc.identifier.citation Huang, 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.issn 1553-7366 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4737682
dc.description.abstract Interferon-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.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi://10.1371/journal.ppat.1001258 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017121/pdf/ en_US
dash.license LAA
dc.subject virology en_US
dc.subject host antiviral responses en_US
dc.subject host invasion and cell entry en_US
dc.title Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Pathogens en_US
dash.depositing.author Farzan, Michael Reynolds
dc.date.available 2011-03-04T17:42:56Z
dash.affiliation.other HMS^Microbiology and Molecular Genetics en_US

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