HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread
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.
open access article
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.
ISSN : 2211-1247
- Leicester School of Pharmacy