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

Coralie Daussy (1) , Mathilde Galais (1) , Baptiste Pradel (1) , Véronique Robert-Hebmann (1) , Sophie Sagnier (1) , Sophie Pattingre (2) , Martine Biard-Piechaczyk (1) , Lucile Espert (1, 3, 4)

1 IRIM - Institut de Recherche en Infectiologie de Montpellier
2 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
3 UM - Université de Montpellier
4 CNRS - Centre National de la Recherche Scientifique

The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4+ T lymphocytes death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers autophagy, process necessary to subsequent apoptosis, and to production of Reactive Oxygen Species (ROS) in bystander CD4+ T cells. Here, we demonstrate that Env-induced oxidative stressisresponsible 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, catalase and PEX14, upon Env exposure, since the down-regulation of either BECLIN 1 or p62/SQSTM1 restores their expression levels. Fluorescence studies allowed us to conclude that Envmediated 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.

Mots clés: Autophagy; HIV-1 Env; ROS; Apoptosis; Peroxisomes; apoptosis; autophagy; peroxisomes

Domaines: Sciences du Vivant [q-bio]

Coralie Daussy, Mathilde Galais, Baptiste Pradel, Véronique Robert-Hebmann, Sophie Sagnier, et al.. HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4 + T cell death. Autophagy, 2020, pp.1-10. ⟨10.1080/15548627.2020.1831814⟩. ⟨hal-02997474⟩