| Title: |
HIV‐1 Vpr inhibits autophagy during the early steps of infection of CD4 T cells |
| Authors: |
Alfaisal, Jamal; Machado, Alice; Galais, Mathilde; Robert‐hebmann, Véronique; Arnauné‐pelloquin, Laetitia; Espert, Lucile; Biard‐piechaczyk, Martine |
| Contributors: |
Institut de Recherche en Infectiologie de Montpellier (IRIM); Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS); Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA); Institut des sciences du cerveau de Toulouse. (ISCT); Université Toulouse - Jean Jaurès (UT2J); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI); Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS); Université de Montpellier (UM); Centre National de la Recherche Scientifique (CNRS); ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010) |
| Source: |
ISSN: 0248-4900. |
| Publisher Information: |
CCSD; Wiley |
| Publication Year: |
2019 |
| Collection: |
Université Toulouse III - Paul Sabatier: HAL-UPS |
| Subject Terms: |
HIV-1; Vpr; FOXO3a; LC3; autophagy; [SDV]Life Sciences [q-bio]; [SDV.BC]Life Sciences [q-bio]/Cellular Biology |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/boc.201900071 |
| Availability: |
https://hal.science/hal-02997501; https://hal.science/hal-02997501v1/document; https://hal.science/hal-02997501v1/file/Biology%20of%20the%20Cell%202019.pdf; https://doi.org/10.1111/boc.201900071 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.8207E994 |
| Database: |
BASE |