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

Abstract : 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. As HIV-1 viral protein R (Vpr) is the only auxiliary protein found within the virion in substantial amount, we studied its capability to control the early steps of HIV-1 envelope-mediated autophagy. Results: We demonstrated that ectopic Vpr inhibits autophagy in both the Jurkat CD4 T cell line and HEK.293T cells. Interestingly, Vpr coming from the virus also blocks autophagy in CD4 T cells, the main cell target of HIV-1. Furthermore, Vpr decreases the expression level of two essential autophagy proteins (ATG), LC3B and Beclin-1, and an important autophagy-related protein, BNIP3 as well as the level of their mRNA. We also demonstrated in HEK.293T cells that Vpr degrades the FOXO3a transcription factor through the ubiquitin proteasome system. Conclusion: Vpr, the only well expressed HIV-1 protein incorporated into viruses, is able to negatively control autophagy induced during HIV-1 entry into CD4 T cells. Significance: We provide insights of how HIV-1 controls autophagy very early after its entry into CD4 T cells and discovered a new function of Vpr. These results open the route to a better understanding of the roles of Vpr during HIV-1 infection through FOXO3a degradation and could be important to consider additional therapies that counteract the role of Vpr on autophagy.
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https://hal.archives-ouvertes.fr/hal-02997501
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Submitted on : Monday, November 16, 2020 - 11:02:38 AM
Last modification on : Thursday, October 14, 2021 - 12:04:03 PM
Long-term archiving on: : Wednesday, February 17, 2021 - 6:39:30 PM

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Jamal Alfaisal, Alice Machado, Mathilde Galais, Véronique Robert‐hebmann, Laetitia Arnauné‐pelloquin, et al.. HIV‐1 Vpr inhibits autophagy during the early steps of infection of CD4 T cells. Biology of the Cell, Wiley, 2019, 111 (12), pp.308-318. ⟨10.1111/boc.201900071⟩. ⟨hal-02997501⟩

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