Selective cell death of latently HIV-infected CD4+ T cells mediated by autosis inducing nanopeptides

Summary

This mechanistic preclinical study seeks to eliminate the resting central-memory CD4 T cells that harbor latent HIV and permit viral rebound after antiretroviral therapy stops. The authors encapsulated two autophagy-inducing peptides, Tat–Beclin 1 and Tat–vFLIP-α2, in biodegradable lipid-coated PLGA nanoparticles for controlled intracellular delivery. A single nanopeptide dose eliminated latent infection in a primary in vitro latency model and ex vivo in resting CD4 cells from people whose virus had been suppressed on therapy for more than a year. Treated latent cells showed LC3B lipidation, SQSTM1/p62 degradation, and increased sodium–potassium ATPase activity, markers consistent with autosis. Silencing ATG5 or ATG7, or inhibiting the ATPase, reversed cell death, supporting the proposed mechanism. No viral rebound was detected after treatment in the reported systems. The principal finding is selective removal of a clinically important latent reservoir through nanoparticle-delivered, ATPase-dependent autophagic cell death. Its significance is a potential kill strategy that does not rely on viral reactivation and may avoid infecting bystander cells. The abstract does not establish selectivity comprehensively, reservoir clearance in vivo, long-term rebound prevention, systemic toxicity, or patient efficacy.