Jolly, CL;
(2017)
HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread.
Cell Reports
, 18
(4)
pp. 1062-1074.
10.1016/j.celrep.2016.12.057.
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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.
| Type: | Article |
|---|---|
| Title: | HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2016.12.057 |
| Publisher version: | http://dx.doi.org/10.1016/j.celrep.2016.12.057 |
| Language: | English |
| Additional information: | ©2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | HIV; T cell; signaling; TCR; phosphoproteomics; synapse |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1538598 |
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