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Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex.

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cam.depositDate2021-12-17
cam.issuedOnline2022-02-01
cam.orpheus.counter1
cam.orpheus.successThu Feb 24 18:06:33 GMT 2022 - Embargo updated*
datacite.ispreviousversionof.handlehttps://www.repository.cam.ac.uk/handle/1810/334699
datacite.issupplementedby.urlhttps://doi.org/10.17863/CAM.79113
dc.contributor.authorNightingale, Katie
dc.contributor.authorPotts, Martin
dc.contributor.authorHunter, Leah M
dc.contributor.authorFielding, Ceri A
dc.contributor.authorZerbe, Cassie M
dc.contributor.authorFletcher-Etherington, Alice
dc.contributor.authorNobre, Luis
dc.contributor.authorWang, Eddie CY
dc.contributor.authorStrang, Blair L
dc.contributor.authorHoughton, Jack W
dc.contributor.authorAntrobus, Robin
dc.contributor.authorSuarez, Nicolas M
dc.contributor.authorNichols, Jenna
dc.contributor.authorDavison, Andrew J
dc.contributor.authorStanton, Richard J
dc.contributor.authorWeekes, Michael
dc.contributor.orcidNightingale, Katie [0000-0001-9958-4699]
dc.contributor.orcidPotts, Martin [0000-0002-6738-0066]
dc.contributor.orcidHunter, Leah M [0000-0002-0000-5712]
dc.contributor.orcidFletcher-Etherington, Alice [0000-0001-7313-9247]
dc.contributor.orcidNobre, Luis [0000-0003-0467-8989]
dc.contributor.orcidWang, Eddie CY [0000-0002-2243-4964]
dc.contributor.orcidStrang, Blair L [0000-0001-9407-1974]
dc.contributor.orcidSuarez, Nicolas M [0000-0001-8429-8374]
dc.contributor.orcidNichols, Jenna [0000-0003-0093-7170]
dc.contributor.orcidDavison, Andrew J [0000-0002-4991-9128]
dc.contributor.orcidStanton, Richard J [0000-0002-6799-1182]
dc.contributor.orcidWeekes, Michael [0000-0003-3196-5545]
dc.date.accessioned2021-12-21T00:31:10Z
dc.date.available2021-12-21T00:31:10Z
dc.date.issued2022-02-08
dc.date.updated2021-12-17T17:20:20Z
dc.description.abstractHuman cytomegalovirus (HCMV) is an important human pathogen and a paradigm of viral immune evasion, targeting intrinsic, innate, and adaptive immunity. We have employed two orthogonal multiplexed tandem mass tag-based proteomic screens to identify host proteins down-regulated by viral factors expressed during the latest phases of viral infection. This approach revealed that the HIV-1 restriction factor Schlafen-11 (SLFN11) was degraded by the poorly characterized, late-expressed HCMV protein RL1, via recruitment of the Cullin4-RING E3 Ubiquitin Ligase (CRL4) complex. SLFN11 potently restricted HCMV infection, inhibiting the formation and spread of viral plaques. Overall, we show that a restriction factor previously thought only to inhibit RNA viruses additionally restricts HCMV. We define the mechanism of viral antagonism and also describe an important resource for revealing additional molecules of importance in antiviral innate immunity and viral immune evasion.
dc.identifier.doi10.17863/CAM.79088
dc.identifier.eissn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331636
dc.language.isoeng
dc.publisherProceedings of the National Academy of Sciences
dc.publisher.departmentDepartment of Medicine
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleHuman cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex.
dc.typeArticle
dcterms.dateAccepted2021-12-14
prism.publicationNameProc Natl Acad Sci U S A
pubs.funder-project-idWellcome Trust (108070/Z/15/Z)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1073/pnas.2108173119

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