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dc.contributor.authorTorres, Alice A
dc.contributor.authorMacilwee, Stephanie L
dc.contributor.authorRashid, Amir
dc.contributor.authorCox, Sarah E
dc.contributor.authorAlbarnaz, Jonas D
dc.contributor.authorBonjardim, Claudio A
dc.contributor.authorSmith, Geoffrey
dc.description.abstractCellular proteins often have multiple and diverse functions. This is illustrated with protein Spir-1 that is an actin nucleator, but, as shown here, also functions to enhance innate immune signalling downstream of RNA sensing by RIG-I/MDA-5. In human and mouse cells lacking Spir-1, IRF3 and NF-κB-dependent gene activation is impaired, whereas Spir-1 overexpression enhanced IRF3 activation. Furthermore, the infectious virus titres and sizes of plaques formed by two viruses that are sensed by RIG-I, vaccinia virus (VACV) and Zika virus, are increased in Spir-1-/- cells. These observations demonstrate the biological importance of Spir-1 in the response to virus infection. Like cellular proteins, viral proteins also have multiple and diverse functions. Here, we also show that VACV virulence factor K7 binds directly to Spir-1 and that a diphenylalanine motif of Spir-1 is needed for this interaction and for Spir-1-mediated enhancement of IRF3 activation. Thus, Spir-1 is a new virus restriction factor and is targeted directly by an immunomodulatory viral protein that enhances virus virulence and diminishes the host antiviral responses.
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.titleThe actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling.
dc.publisher.departmentDepartment of Pathology
prism.publicationNamePLoS Pathog
dc.contributor.orcidTorres, Alice A [0000-0003-2352-2584]
dc.contributor.orcidMacilwee, Stephanie L [0000-0003-2532-9745]
dc.contributor.orcidRashid, Amir [0000-0001-8119-4967]
dc.contributor.orcidCox, Sarah E [0000-0001-9982-3987]
dc.contributor.orcidAlbarnaz, Jonas D [0000-0002-8792-813X]
dc.contributor.orcidSmith, Geoffrey [0000-0002-3730-9955]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (090315/B/09/A)
pubs.funder-project-idIsaac Newton Trust (18.07i(j))
pubs.funder-project-idWellcome Trust (090315/Z/09/Z)
cam.orpheus.successThu Feb 24 18:06:44 GMT 2022 - Embargo updated*
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International