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

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.

HIV-1 Vpr inhibits autophagy during the early steps of infection of CD4 T cells.

Background Information: Autophagy is induced during HIV-1 entry into CD4 T cells by the fusion of the membranes triggered by the gp41 envelope glycoprotein. This anti-HIV-1 mechanism is inhibited by the viral infectivity factor (Vif) neosynthesized after HIV-1 integration to allow viral replication. However, autophagy is very rapidly controlled after HIV-1 entry by a still unknown mechanism.

[LAP (LC3-associated phagocytosis): phagocytosis or autophagy?].

Phagocytosis and macroautophagy, named here autophagy, are two essential mechanisms of lysosomal degradation of diverse cargos into membrane structures. Both mechanisms are involved in immune regulation and cell survival. However, phagocytosis triggers degradation of extracellular material whereas autophagy engulfs only cytoplasmic elements.

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic.

In untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4 T cell counts. HIV-1 envelope glycoprotein complex (Env) is a major cytopathic determinant in viral replication; therefore, we have deeply characterized Env function in this rare clinical phenotype.

[Autophagy, ATG proteins and infectious diseases].

One of the main functions of the autophagy pathway is to control infections. Intracellular micro-organisms or their products once internalized in the host cell can be directly degraded by autophagy, a process called xenophagy. Autophagy is also involved in other innate immune responses and participates to the adaptive immune system.