共 55 条
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
来源:
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.
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页码:275 / 286
页数:12
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