Anti-apoptotic Protein BIRC5 Maintains Survival of HIV-1-Infected CD4 T Cells.

Immunity
Authors
Keywords
Abstract

HIV-1 infection of CD4 T cells leads to cytopathic effects and cell demise, which is counter to the observation that certain HIV-1-infected cells possess a remarkable long-term stability and can persist lifelong in infected individuals treated with suppressive antiretroviral therapy (ART). Using quantitative mass spectrometry-based proteomics, we showed that HIV-1 infection activated cellular survival programs that were governed by BIRC5, a molecular inhibitor of cell apoptosis that is frequently overexpressed in malignant cells. BIRC5 and its upstream regulator OX40 were upregulated in productively and latently infected CD4 T cells and were functionally involved in maintaining their viability. Moreover, OX40-expressing CD4 T cells from ART-treated patients were enriched for clonally expanded HIV-1 sequences, and pharmacological inhibition of BIRC5 resulted 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 may lead to clinical strategies to reduce persisting viral reservoirs.

Year of Publication
2018
Journal
Immunity
Volume
48
Issue
6
Pages
1183-1194.e5
Date Published
2018 06 19
ISSN
1097-4180
DOI
10.1016/j.immuni.2018.04.004
PubMed ID
29802019
PubMed Central ID
PMC6013384
Links
Grant list
R21 AI106468 / AI / NIAID NIH HHS / United States
R01 AI078799 / AI / NIAID NIH HHS / United States
R01 HL134539 / HL / NHLBI NIH HHS / United States
U01 AI114235 / AI / NIAID NIH HHS / United States
R01 AI098487 / AI / NIAID NIH HHS / United States
R01 AI130005 / AI / NIAID NIH HHS / United States
U01 AI117841 / AI / NIAID NIH HHS / United States
R56 AI125109 / AI / NIAID NIH HHS / United States
R33 AI116228 / AI / NIAID NIH HHS / United States
R21 AI124776 / AI / NIAID NIH HHS / United States
R01 AI120008 / AI / NIAID NIH HHS / United States
R21 AI116228 / AI / NIAID NIH HHS / United States
S10 OD012027 / OD / NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States