Show simple item record

dc.contributor.authorGabaev, Ildar
dc.contributor.authorWilliamson, James
dc.contributor.authorCrozier, Thomas
dc.contributor.authorSchulz, Thomas F
dc.contributor.authorLehner, Paul
dc.date.accessioned2020-09-23T23:30:52Z
dc.date.available2020-09-23T23:30:52Z
dc.date.issued2020-10-13
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/310646
dc.description.abstractKaposi's sarcoma herpesvirus (KSHV) is an oncogenic human virus and the leading cause of mortality in HIV infection. KSHV reactivation from latent- to lytic-stage infection initiates a cascade of viral gene expression. Here we show how these changes remodel the host cell proteome to enable viral replication. By undertaking a systematic and unbiased analysis of changes to the endothelial cell proteome following KSHV reactivation, we quantify >7,000 cellular proteins and 71 viral proteins and provide a temporal profile of protein changes during the course of lytic KSHV infection. Lytic KSHV induces >2-fold downregulation of 291 cellular proteins, including PKR, the key cellular sensor of double-stranded RNA. Despite the multiple episomes per cell, CRISPR-Cas9 efficiently targets KSHV genomes. A complementary KSHV genome-wide CRISPR genetic screen identifies K5 as the viral gene responsible for the downregulation of two KSHV targets, Nectin-2 and CD155, ligands of the NK cell DNAM-1 receptor.
dc.description.sponsorshipHorizon 2020/grant agreement no. 656511 Deutsche Forschungsgemeinschaft – SFB900/3 – 158989968; project C1.
dc.format.mediumPrint
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International (CC BY)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCell Line
dc.subjectEndothelial Cells
dc.subjectHumans
dc.subjectHerpesvirus 8, Human
dc.subjectSarcoma, Kaposi
dc.subjectDNA-Directed DNA Polymerase
dc.subjecteIF-2 Kinase
dc.subjectProteome
dc.subjectViral Proteins
dc.subjectAntigens, Differentiation, T-Lymphocyte
dc.subjectLigands
dc.subjectProteomics
dc.subjectVirus Activation
dc.subjectDown-Regulation
dc.subjectUp-Regulation
dc.subjectKinetics
dc.subjectMutation
dc.subjectGene Library
dc.subjectGenes, Viral
dc.subjectGenetic Testing
dc.subjectImmunomodulation
dc.subjectGene Ontology
dc.titleQuantitative Proteomics Analysis of Lytic KSHV Infection in Human Endothelial Cells Reveals Targets of Viral Immune Modulation.
dc.typeArticle
prism.issueIdentifier2
prism.publicationDate2020
prism.publicationNameCell Rep
prism.startingPage108249
prism.volume33
dc.identifier.doi10.17863/CAM.57744
dcterms.dateAccepted2020-09-17
rioxxterms.versionofrecord10.1016/j.celrep.2020.108249
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-10
dc.contributor.orcidWilliamson, James [0000-0002-2009-189X]
dc.contributor.orcidCrozier, Thomas [0000-0003-0951-4588]
dc.contributor.orcidLehner, Paul [0000-0001-9383-1054]
dc.identifier.eissn2211-1247
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEuropean Commission (656511)
pubs.funder-project-idMedical Research Council (MR/R001405/1)
cam.orpheus.successThu Nov 05 11:51:17 GMT 2020 - The item has an open VoR version.
cam.orpheus.counter4
rioxxterms.freetoread.startdate2100-01-01


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

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