Killing HIV-infected resting central memory CD4(+) T cells by targeting inhibitor of apoptosis proteins-inhibited autophagy

Dysfunction of CD4(+) T cells by HIV infection can cause serious immune defects. Recently, Campbell and colleagues described an intriguing and simple therapeutic method for HIV-infected resting central memory CD4(+) T cells (HIV-T(CM)), dependently on inhibitor of apoptosis (IAP) family proteins-targeted and second mitochondria-derived activator of caspases (SMAC) mimetics-mediated apoptosis, which is only triggered in HIV-T(CM) and not uninfected ones. Autophagy induction and subsequent formation of a ripoptosome-like death signaling complex were observed after such treatment, which may partially explain the potential mechanism. However, the direct intracellular inhibitory effects of IAPs on autophagy, as well as the critical roles of autophagy in activating extracellular anti-infection immune responses, warrant further investigation. Thus, this pointer aims to provide potential alternative mechanisms and to suggest important avenues for follow-up study.