The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking.
The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking.
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DOI：
10.1083/jcb.201503124
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发表时间：
2015-10-26
期刊：
影响因子：
--
通讯作者：
Niedergang F
中科院分区：
文献类型：
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作者：
Dumas A;Lê-Bury G;Marie-Anaïs F;Herit F;Mazzolini J;Guilbert T;Bourdoncle P;Russell DG;Benichou S;Zahraoui A;Niedergang F
The HIV protein Vpr interacts with EB1, p150Glued, and dynein heavy chain and perturbs the centripetal movement of phagosomes and their maturation, resulting in impaired phagolysosome biogenesis, which is important for bacterial clearance and cytokine production. Human immunodeficiency virus type 1 (HIV-1) impairs major functions of macrophages but the molecular basis for this defect remains poorly characterized. Here, we show that macrophages infected with HIV-1 were unable to respond efficiently to phagocytic triggers and to clear bacteria. The maturation of phagosomes, defined by the presence of late endocytic markers, hydrolases, and reactive oxygen species, was perturbed in HIV-1–infected macrophages. We showed that maturation arrest occurred at the level of the EHD3/MICAL-L1 endosomal sorting machinery. Unexpectedly, we found that the regulatory viral protein (Vpr) was crucial to perturb phagosome maturation. Our data reveal that Vpr interacted with EB1, p150Glued, and dynein heavy chain and was sufficient to critically alter the microtubule plus end localization of EB1 and p150Glued, hence altering the centripetal movement of phagosomes and their maturation. Thus, we identify Vpr as a modulator of the microtubule-dependent endocytic trafficking in HIV-1–infected macrophages, leading to strong alterations in phagolysosome biogenesis.
