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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.issuedOnline2022-02
cam.oa.sapoa_rrs_na
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 P
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 P [0000-0003-3196-5545]
dc.date.accessioned2022-03-06T02:02:30Z
dc.date.available2022-03-06T02:02:30Z
dc.date.issued2022-02-08
dc.date.updated2022-03-06T02:02:28Z
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.82117
dc.identifier.eissn1091-6490
dc.identifier.issn0027-8424
dc.identifier.otherPMC8832970
dc.identifier.other35105802
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334699
dc.languageeng
dc.language.isoeng
dc.publisherProceedings of the National Academy of Sciences
dc.publisher.urlhttp://dx.doi.org/10.1073/pnas.2108173119
dc.rightsAll Rights Reserved
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/
dc.sourcenlmid: 7505876
dc.sourceessn: 1091-6490
dc.subjectSchlafen
dc.subjecthost–pathogen interaction
dc.subjecthuman cytomegalovirus
dc.subjectinnate immunity
dc.subjectrestriction factor
dc.subjectCytomegalovirus
dc.subjectCytomegalovirus Infections
dc.subjectHumans
dc.subjectImmune Evasion
dc.subjectNuclear Proteins
dc.subjectProteolysis
dc.subjectUbiquitin-Protein Ligase Complexes
dc.subjectViral Envelope Proteins
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.issueIdentifier6
prism.publicationNameProc Natl Acad Sci U S A
prism.volume119
pubs.funder-project-idWellcome Trust (108070/Z/15/Z)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1073/pnas.2108173119

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