HIV-1 viral infectivity factor interacts with microtubule-associated protein light chain 3 and inhibits autophagy

被引:50
作者
Borel, Sophie [1 ,2 ]
Robert-Hebmann, Veronique [1 ,2 ]
Alfaisal, Jamal [1 ,2 ]
Jain, Ashish [3 ]
Faure, Mathias [4 ,5 ,6 ,7 ,8 ,9 ]
Espert, Lucile [1 ,2 ]
Chaloin, Laurent [1 ,2 ]
Paillart, Jean-Christophe [10 ]
Johansen, Terje [3 ]
Biard-Piechaczyk, Martine [1 ,2 ]
机构
[1] CNRS, Ctr Etud Agents Pathogenes & Biotechnol Sante CPB, F-34293 Montpellier 5, France
[2] Univ Montpellier, F-34059 Montpellier, France
[3] Arctic Univ Norway, Univ Tromso, Mol Canc Res Grp, Tromso, Norway
[4] Univ Lyon, CIRI, Lyon, France
[5] INSERM, U1111, F-69008 Lyon, France
[6] Ecole Normale Super Lyon, F-69364 Lyon, France
[7] Univ Lyon 1, Ctr Int Rech Infectiol, F-69365 Lyon, France
[8] INSERM, U851, CNRS, UMR5308, F-69008 Lyon, France
[9] Univ Lyon, Lyon, France
[10] Univ Strasbourg, Inst Biol Mol & Cellulaire, CNRS, Architecture & React ARN, Strasbourg, France
关键词
APOBEC3G; autophagy; HIV; microtubule-associated protein light chain 3; viral infectivity factor; HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1; VIF; APOBEC3G BINDING; STRUCTURAL BASIS; ENZYME APOBEC3G; E3; LIGASE; T-CELLS; MOTIF; MULTIMERIZATION; IDENTIFICATION;
D O I
10.1097/QAD.0000000000000554
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. Design/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. Conclusion: Our study unveils that Vif inhibits autophagy independently of its action on APOBEC3Gand, therefore, suggest a newfunction of this viral protein in restricting innate antiviral mechanisms. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
引用
收藏
页码:275 / 286
页数:12
相关论文
共 55 条
[1]   ATG8 Family Proteins Act as Scaffolds for Assembly of the ULK Complex SEQUENCE REQUIREMENTS FOR LC3-INTERACTING REGION (LIR) MOTIFS [J].
Alemu, Endalkachew Ashenafi ;
Lamark, Trond ;
Torgersen, Knut Martin ;
Birgisdottir, Aasa Birna ;
Larsen, Kenneth Bowitz ;
Jain, Ashish ;
Olsvik, Hallvard ;
Overvatn, Aud ;
Kirkin, Vladimir ;
Johansen, Terje .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (47) :39275-39290
[2]   Network organization of the human autophagy system [J].
Behrends, Christian ;
Sowa, Mathew E. ;
Gygi, Steven P. ;
Harper, J. Wade .
NATURE, 2010, 466 (7302) :68-U84
[3]   The SOCS-Box of HIV-1 Vif Interacts with ElonginBC by Induced-Folding to Recruit Its Cul5-Containing Ubiquitin Ligase Complex [J].
Bergeron, Julien R. C. ;
Huthoff, Hendrik ;
Veselkov, Dennis A. ;
Beavil, Rebecca L. ;
Simpson, Peter J. ;
Matthews, Stephen J. ;
Malim, Michael H. ;
Sanderson, Mark R. .
PLOS PATHOGENS, 2010, 6 (06)
[4]   Importance of the proline-rich multimerization domain on the oligomerization and nucleic acid binding properties of HIV-1 Vif [J].
Bernacchi, Serena ;
Mercenne, Gaelle ;
Tournaire, Clemence ;
Marquet, Roland ;
Paillart, Jean-Christophe .
NUCLEIC ACIDS RESEARCH, 2011, 39 (06) :2404-2415
[5]   APOBEC3G Restricts HIV-1 to a Greater Extent than APOBEC3F and APOBEC3DE in Human Primary CD4+ T Cells and Macrophages [J].
Chaipan, Chawaree ;
Smith, Jessica L. ;
Hu, Wei-Shau ;
Pathak, Vinay K. .
JOURNAL OF VIROLOGY, 2013, 87 (01) :444-453
[6]   Identification of a Novel WxSLVK Motif in the N Terminus of Human Immunodeficiency Virus and Simian Immunodeficiency Virus Vif That Is Critical for APOBEC3G and APOBEC3F Neutralization [J].
Dang, Ying ;
Wang, Xiaojun ;
Zhou, Tao ;
York, Ian A. ;
Zheng, Yong-Hui .
JOURNAL OF VIROLOGY, 2009, 83 (17) :8544-8552
[7]   HIV-1 gp41 fusogenic function triggers autophagy in uninfected cells [J].
Denizot, Melanie ;
Varbanov, Mihayl ;
Espert, Lucile ;
Robert-Hebmann, Veronique ;
Sagnier, Sophie ;
Garcia, Elisabet ;
Curriu, Marta ;
Mamoun, Robert ;
Blanco, Julia ;
Biard-Piechaczyk, Martine .
AUTOPHAGY, 2008, 4 (08) :998-1008
[8]   Autophagy, Immunity, and Microbial Adaptations [J].
Deretic, Vojo ;
Levine, Beth .
CELL HOST & MICROBE, 2009, 5 (06) :527-549
[9]   The HIV-1 Vif PPLP motif is necessary for human APOBEC3G binding and degradation [J].
Donahue, John P. ;
Vetter, Michael L. ;
Mukhtar, Nizar A. ;
D'Aquila, Richard T. .
VIROLOGY, 2008, 377 (01) :49-53
[10]   Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4 [J].
Espert, Lucile ;
Denizot, Melanie ;
Grimaldi, Marina ;
Robert-Hebmann, Veronique ;
Gay, Bernard ;
Varbanov, Mihayl ;
Codogno, Patrice ;
Biard-Piechaczyk, Martine .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (08) :2161-2172