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dc.contributor.authorStarling, Shimona
dc.contributor.authorShivkumar, Maitreyi
dc.contributor.authorJolly, Clare
dc.contributor.authorLen, Alice C.L.
dc.date.accessioned2019-10-15T08:24:12Z
dc.date.available2019-10-15T08:24:12Z
dc.date.issued2017-01-24
dc.identifier.citationLen, A.C.L., Shivkumar, M., Jolly, C., (2017) HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread. Cell Reports, 18(4), pp.1062–1074.en
dc.identifier.issn2211-1247
dc.identifier.urihttps://dora.dmu.ac.uk/handle/2086/18612
dc.descriptionopen access articleen
dc.description.abstractHIV-1 spreads between CD4 T cells most efficiently through virus-induced cell-cell contacts. To test whether this process potentiates viral spread by activating signaling pathways, we developed an approach to analyze the phosphoproteome in infected and uninfected mixed-population T cells using differential metabolic labeling and mass spectrometry. We discovered HIV-1-induced activation of signaling networks during viral spread encompassing over 200 cellular proteins. Strikingly, pathways downstream of the T cell receptor were the most significantly activated, despite the absence of canonical antigen-dependent stimulation. The importance of this pathway was demonstrated by the depletion of proteins, and we show that HIV-1 Env-mediated cell-cell contact, the T cell receptor, and the Src kinase Lck were essential for signaling-dependent enhancement of viral dissemination. This study demonstrates that manipulation of signaling at immune cell contacts by HIV-1 is essential for promoting virus replication and defines a paradigm for antigen-independent T cell signaling.en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectHIVen
dc.subjectT cellen
dc.subjectsignalingen
dc.subjectTCRen
dc.subjectphosphoproteomicsen
dc.subjectsynapseen
dc.titleHIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spreaden
dc.typeArticleen
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2016.12.057
dc.funderWellcome Trusten
dc.cclicenceCC-BY-NCen
dc.date.acceptance2016-12-16
dc.exception.ref2021codes254aen
dc.funder.otherMedical Research Council (MRC)en


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