HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death.

HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death. Autophagy. 2020 Oct 19;:1-10 Authors: Daussy CF, Galais M, Pradel B, Robert-Hebmann V, Sagnier S, Pattingre S, Biard-Piechaczyk M, Espert L Abstract The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4+ T lymphocyte cell death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers macroautophagy/autophagy, a process necessary for subsequent apoptosis, and the production of reactive oxygen species (ROS) in bystander CD4+ T cells. Here, we demonstrate that Env-induced oxidative stress is responsible for their death by apoptosis. Moreover, we report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy. Indeed, we observe a selective autophagy-dependent decrease in the expression of peroxisomal proteins, CAT and PEX14, upon Env exposure; the downregulation of either BECN1 or SQSTM1/p62 restores their expression levels. Fluorescence studies allowed us to conclude that Env-mediated autophagy degrades these entire organelles and specifically the mature ones. Together, our results on Env-induced pexophagy provide new clues on HIV-1-induced immunodeficiency. Abbreviations: Ab: antibodies; AF: auranofin; AP: anti-proteases; ART: antiretroviral therapy; BafA1: bafilomycin A1...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research