HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread.
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ABSTRACT:
SUBMITTER: Len ACL
PROVIDER: S-EPMC5289937 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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 T cell receptor were the most significantly activated, despite the absence of canonical antigen dependent stimulation. The importance of this pathway was demonstrated by depletion of proteins and we show that HIV-1 Env mediated cell-cell contact, 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 new paradigm for antigen independent T cell signaling.
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