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dc.contributor.authorNobre, Luis V
dc.contributor.authorNightingale, Katie
dc.contributor.authorRavenhill, Benjamin J
dc.contributor.authorAntrobus, Robin
dc.contributor.authorSoday, Lior
dc.contributor.authorNichols, Jenna
dc.contributor.authorDavies, James A
dc.contributor.authorSeirafian, Sepehr
dc.contributor.authorWang, Eddie CY
dc.contributor.authorDavison, Andrew J
dc.contributor.authorWilkinson, Gavin WG
dc.contributor.authorStanton, Richard J
dc.contributor.authorHuttlin, Edward L
dc.contributor.authorWeekes, Michael P
dc.date.accessioned2020-01-15T05:13:42Z
dc.date.available2020-01-15T05:13:42Z
dc.date.issued2019-12-24
dc.date.submitted2019-07-03
dc.identifier.other49894
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/300896
dc.description.abstractHuman cytomegalovirus (HCMV) extensively modulates host cells, downregulating >900 human proteins during viral replication and degrading ≥133 proteins shortly after infection. The mechanism of degradation of most host proteins remains unresolved, and the functions of many viral proteins are incompletely characterised. We performed a mass spectrometry-based interactome analysis of 169 tagged, stably-expressed canonical strain Merlin HCMV proteins, and two non-canonical HCMV proteins, in infected cells. This identified a network of >3400 virus-host and >150 virus-virus protein interactions, providing insights into functions for multiple viral genes. Domain analysis predicted binding of the viral UL25 protein to SH3 domains of NCK Adaptor Protein-1. Viral interacting proteins were identified for 31/133 degraded host targets. Finally, the uncharacterised, non-canonical ORFL147C protein was found to interact with elements of the mRNA splicing machinery, and a mutational study suggested its importance in viral replication. The interactome data will be important for future studies of herpesvirus infection.
dc.languageen
dc.subjectTools and Resources
dc.subjectComputational and Systems Biology
dc.subjectMicrobiology and Infectious Disease
dc.subjectproteomics
dc.subjectsystems virology
dc.subjecthuman cytomegalovirus
dc.subjecthost-pathogen interaction
dc.subjectimmune evasion
dc.subjectprotein-protein interaction
dc.subjectHuman
dc.subjectVirus
dc.titleHuman cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions
dc.typeArticle
dc.date.updated2020-01-15T05:13:41Z
dc.identifier.doi10.17863/CAM.47971
dcterms.dateAccepted2019-12-24
rioxxterms.versionofrecord10.7554/elife.49894
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisorsenior_editor: Garrett, Wendy S
datacite.contributor.supervisoreditor: Maes, Piet
dc.contributor.orcidNobre, Luis V [0000-0003-0467-8989]
dc.contributor.orcidNightingale, Katie [0000-0001-9958-4699]
dc.contributor.orcidSoday, Lior [0000-0001-6927-2985]
dc.contributor.orcidDavies, James A [0000-0003-3569-4500]
dc.contributor.orcidWang, Eddie CY [0000-0002-2243-4964]
dc.contributor.orcidDavison, Andrew J [0000-0002-4991-9128]
dc.contributor.orcidWilkinson, Gavin WG [0000-0002-5623-0126]
dc.contributor.orcidStanton, Richard J [0000-0002-6799-1182]
dc.contributor.orcidHuttlin, Edward L [0000-0002-1822-1173]
dc.contributor.orcidWeekes, Michael P [0000-0003-3196-5545]
dc.identifier.eissn2050-084X
pubs.funder-project-idWellcome (108070/Z/15/Z)
pubs.funder-project-idMedical Research Council (MR/L018373/1)
pubs.funder-project-idMedical Research Council (MR/P001602/1)
pubs.funder-project-idWellcome (WT090323MA)
pubs.funder-project-idMedical Research Council (MC_UU_12014/3)
pubs.funder-project-idNational Institutes of Health (U24 HG006673)
pubs.funder-project-idMedical Research Council (MR/S00971X/1)


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