HIV-1 viral infectivity factor interacts with microtubule-associated protein light chain 3 and inhibits autophagy. (28th January 2015)

• Record Type: Journal Article
• Authors: Borel, Sophie; Robert-Hebmann, Véronique; Alfaisal, Jamal; Jain, Ashish; Faure, Mathias; Espert, Lucile; Chaloin, Laurent; Paillart, Jean-Christophe; Johansen, Terje; Biard-Piechaczyk, Martine
• Is Part Of: AIDS. Volume 29:Number 3(2015)
• Publication Date: 2015-01-28
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000554
• Languages: English
• ISSNs: 0269-9370

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>Autophagy, an important antiviral process triggered during HIV-1 entry by gp41-dependent membrane fusion, is repressed in infected CD4<sup>+</sup> 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.</p> </sec> <sec> <title>Design/methods:</title> <p>To determine the role of Vif in autophagy inhibition, we used cell lines that express CD4 and CXCR4 and primary CD4<sup>+</sup> 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 (NL4.3ΔVif), or after exogenous Vif expression.</p> </sec> <sec> <title>Results:</title> <p>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 NL4.3ΔVif, but prevented in cells infected by NL4.3. Furthermore, autophagy triggered in NL4.3ΔVif-infected cells is inhibited when Vif is expressed in <italic>trans</italic> but is still active when target cells express a mutant of Vif that binds weakly to LC3B.</p> </sec> <sec> <title>Conclusion:</title> <p>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.</p> </sec> </abstract>