SMAC Mimetics Induce Autophagy-Dependent Apoptosis of HIV-1-Infected Resting Memory CD4+ T Cells.

ABSTRACT: Long-lived resting memory CD4+ T cells (T_CM) are a major reservoir of latent HIV infection. We hypothesized that latent HIV-T_CM cells are maintained by aberrant expression of cell survival factors, including XIAP, BIRC2/cIAP1, and beclin-1. DIABLO/SMAC mimetics are therapeutic agents that compromise cell survival by hijacking host apoptotic machinery. We found that DIABLO/SMAC mimetics (birinapant, GDC-0152, and embelin) selectively kill HIV-T_CM without increasing virus production or targeting uninfected T_CM. Treatment of HIV-T_CM with DIABLO/SMAC mimetics promoted XIAP and BIRC2 degradation, which triggered autophagy and the formation of a cell death complex consisting of pro-apoptotic (FADD, RIPK1, RIPK3, and caspase 8) and autophagy

SUBMITTER: Campbell GR 

PROVIDER: S-EPMC6250054 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature