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J Cell Biol. 2015 Oct 26;211(2):359-72. doi: 10.1083/jcb.201503124.

The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking.

Author information

1
Institut National de la Santé et de la Recherche Médicale U1016, Institut Cochin, Paris, France Centre National de la Recherche Scientifique UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
2
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
3
Institut National de la Santé et de la Recherche Médicale U1016, Institut Cochin, Paris, France Centre National de la Recherche Scientifique UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France florence.niedergang@inserm.fr.

Abstract

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, p150(Glued), and dynein heavy chain and was sufficient to critically alter the microtubule plus end localization of EB1 and p150(Glued), 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.

PMID:
26504171
PMCID:
PMC4621833
DOI:
10.1083/jcb.201503124
[Indexed for MEDLINE]
Free PMC Article

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