title: HIV-1 viral infectivity factor interacts with microtubule-associated protein light chain 3 and inhibits autophagy.
abstract: OBJECTIVE
  Autophagy, an important antiviral process triggered during HIV-1 entry by gp41-dependent membrane fusion, is repressed in infected CD4+ T cells by an unknown mechanism. The aim of this study was to identify the role of viral infectivity factor (Vif) in the autophagy blockade.
  
  
  METHODS
  To determine the role of Vif in autophagy inhibition, we used cell lines that express CD4 and CXCR4 and primary CD4+ T cells. Pull-down experiments, immunoprecipitation assays and computational analyses were performed to analyze the interaction between Vif and microtubule-associated protein light chain 3B (LC3B), a major autophagy component, in presence or absence of the antiviral host factor apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G), after HIV-1 infection or ectopic expression of Vif. Autophagy was analyzed after infection by viruses expressing Vif (NL4.3) or not (NL4.3[DELTA]Vif), or after exogenous Vif expression.
  
  
  RESULTS
  We demonstrate that the C-terminal part of Vif interacts directly with LC3B, independently of the presence of APOBEC3G.Vif binds to pro-LC3 and autophagy-related protein 4-cleaved LC3 forms, and glycine 120, the amino acid conjugated to phosphatidylethanolamine on autophagosomes, is required. Importantly, we evidence that Vif inhibits autophagy during HIV-1 infection. Indeed, autophagy is detected in target cells infected by NL4.3[DELTA]Vif, but prevented in cells infected by NL4.3. Furthermore, autophagy triggered in NL4.3[DELTA]Vif-infected cells is inhibited when Vif is expressed in trans but is still active when target cells express a mutant of Vif that binds weakly to LC3B.
  
  
  CONCLUSIONS
  Our study unveils that Vif inhibits autophagy independently of its action on APOBEC3G and, therefore, suggest a new function of this viral protein in restricting innate antiviral mechanisms.
authors.forename: Sophie
authors.initials: S
authors.lastname: Borel
authors.forename: Véronique
authors.initials: V
authors.lastname: Robert-Hebmann
authors.forename: Jamal
authors.initials: J
authors.lastname: Alfaisal
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.forename: Mathias
authors.initials: M
authors.lastname: Faure
authors.forename: Lucile
authors.initials: L
authors.lastname: Espert
authors.forename: Laurent
authors.initials: L
authors.lastname: Chaloin
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Paillart
authors.forename: Terje
authors.initials: T
authors.lastname: Johansen
authors.forename: Martine
authors.initials: M
authors.lastname: Biard-Piechaczyk
mesh_terms: D001343:Autophagy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D002498:Centrifugation; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1