HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread
dc.cclicence | CC-BY-NC | en |
dc.contributor.author | Starling, Shimona | |
dc.contributor.author | Shivkumar, Maitreyi | |
dc.contributor.author | Jolly, Clare | |
dc.contributor.author | Len, Alice C.L. | |
dc.date.acceptance | 2016-12-16 | |
dc.date.accessioned | 2019-10-15T08:24:12Z | |
dc.date.available | 2019-10-15T08:24:12Z | |
dc.date.issued | 2017-01-24 | |
dc.description | open access article | en |
dc.description.abstract | HIV-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.exception.ref2021codes | 254a | en |
dc.funder | Wellcome Trust | en |
dc.funder.other | Medical Research Council (MRC) | en |
dc.identifier.citation | Len, 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.doi | https://doi.org/10.1016/j.celrep.2016.12.057 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://dora.dmu.ac.uk/handle/2086/18612 | |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.subject | HIV | en |
dc.subject | T cell | en |
dc.subject | signaling | en |
dc.subject | TCR | en |
dc.subject | phosphoproteomics | en |
dc.subject | synapse | en |
dc.title | HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread | en |
dc.type | Article | en |