DIABLO/SMAC mimetics selectively kill HIV-1-infected resting memory CD4⁺ T cells: a potential role in a cure strategy for HIV-1 infection

Figures & data

Figure 1. SMAC mimetics promote apoptosis in HIV-T_CM via the autophagy-dependent formation of a CASP8-activating platform on phagophore membranes. Treatment of a heterogeneous population of uninfected and latent HIV-infected T_CM with DIABLO/SMAC mimetics induces the degradation of XIAP and BIRC2. This triggers the induction of autophagy and the formation of a cell death complex consisting of pro-apoptotic (FADD, RIPK1, RIPK3, CASP8) and autophagy (ATG5, ATG7 and SQSTM1) proteins on unclosed autophagosomal/phagophore structures in HIV-T_CM, but not uninfected T_CM resulting in the selective apoptosis of only the infected HIV-T_CM, while sparing uninfected bystander cells in the absence of viral activation.