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Immunity. 2018 Jun 19;48(6):1183-1194.e5. doi: 10.1016/j.immuni.2018.04.004. Epub 2018 May 22.

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

Author information

1
Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
2
Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
3
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
4
Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
5
National Institute of Allergies and Infectious Diseases, Bethesda, MD 20892, USA.
6
Buck Institute for Research on Aging, Novato, CA 94945, USA.
7
Infectious Disease Division, Massachusetts General Hospital, Boston, MA 02114, USA.
8
Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: mlichterfeld@partners.org.

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.

KEYWORDS:

BIRC5; HIV-1; OX40; Survivin; apoptosis; clonal proliferation; latency; proteomics; viral reservoirs

Comment in

PMID:
29802019
PMCID:
PMC6013384
DOI:
10.1016/j.immuni.2018.04.004
[Indexed for MEDLINE]
Free PMC Article

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