Proteomics

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BIRC5 maintains survival of HIV-1 infected CD4 T cells


ABSTRACT: Kuo H, Ahmad R, Lee GQ, Chen H, Ouyang Z, Szucs MJ, Kim D, Tsibris A, Chun T, Battivelli E, Verdin E, Rosenberg ES, Carr SA, Yu XG, Lichterfeld M. Immunity 2018. HIV-1 infection of CD4 T cells leads to cytopathic effects and cell demise, which is counterintuitive to the observation that certain HIV-1-infected cells possess a remarkable long-term stability and can persist for decades in infected individuals treated with suppressive antiretroviral therapy (ART). Using quantitative mass spectrometry-based proteomics, we show that HIV-1 infection can activate cellular survival programs that are governed by BIRC5, a molecular inhibitor of cell apoptosis that is frequently over-expressed in malignant cells. BIRC5 and its upstream regulator OX40 are upregulated in productively and latently infected CD4 T cells, and are functionally involved in maintaining their integrity and viability. Moreover, OX40-expressing CD4 T cells from ART-treated patients are strongly enriched for sequence-intact HIV-1, and pharmaceutical inhibition of BIRC5 results in a selective decrease of HIV-1-infected cells in vitro. Together, these findings suggest that BIRC5 supports long-term survival of HIV-1-infected cells and offer new perspectives for clinical strategies to reduce persisting viral reservoirs.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Steven A. Carr  

PROVIDER: MSV000082229 | MassIVE | Mon Apr 02 07:11:00 BST 2018

REPOSITORIES: MassIVE

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