PMID:22072966

Citation	Caillet, M, Janvier, K, Pelchen-Matthews, A, Delcroix-Genête, D, Camus, G, Marsh, M and Berlioz-Torrent, C (2011) Rab7A is required for efficient production of infectious HIV-1. PLoS Pathog. 7:e1002347
Abstract	Retroviruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Rab proteins regulate specific steps in intracellular membrane trafficking by recruiting tethering, docking and fusion factors, as well as the actin- and microtubule-based motor proteins that facilitate vesicle traffic. Using virological tests and RNA interference targeting Rab proteins, we demonstrate that the late endosome-associated Rab7A is required for HIV-1 propagation. Analysis of the late steps of the HIV infection cycle shows that Rab7A regulates Env processing, the incorporation of mature Env glycoproteins into viral particles and HIV-1 infectivity. We also show that siRNA-mediated Rab7A depletion induces a BST2/Tetherin phenotype on HIV-1 release. BST2/Tetherin is a restriction factor that impedes HIV-1 release by tethering mature virus particles to the plasma membrane. Our results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release. Altogether, our results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle.
Links	PubMed PMC3207927 Online version:10.1371/journal.ppat.1002347
Keywords	Antigens, CD/biosynthesis; Antigens, CD/metabolism; Cell Membrane/metabolism; Cell Membrane/virology; Endosomes/metabolism; GPI-Linked Proteins/biosynthesis; GPI-Linked Proteins/metabolism; HEK293 Cells; HIV-1/genetics; HIV-1/growth & development; HIV-1/metabolism; HeLa Cells; Human Immunodeficiency Virus Proteins/metabolism; Humans; Protein Transport; RNA Interference; RNA, Small Interfering; Viral Regulatory and Accessory Proteins/metabolism; Virus Release; env Gene Products, Human Immunodeficiency Virus/biosynthesis; env Gene Products, Human Immunodeficiency Virus/metabolism; rab GTP-Binding Proteins/genetics; rab GTP-Binding Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:RAB7A	involved_in	GO:0045732: positive regulation of protein catabolic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:RAB7A		GO:0045732: positive regulation of protein catabolic process	ECO:0000315:		P		Fig. 6A, and Fig. 7A	complete CACAO 3057
HUMAN:RAB7A		GO:0009405: pathogenesis	ECO:0000315:		P		Fig. 2C	complete CACAO 3059
HUMAN:RAB7A		GO:0019076: release of virus from host	ECO:0000315:		P		Fig. 2AB and Fig. 5	complete CACAO 3060
HUMAN:RAB7A		GO:0048524: positive regulation of viral reproduction	ECO:0000315:		P		Fig. 1A, 1B	complete CACAO 3061
HUMAN:RAB7A	involved_in	GO:0048524: positive regulation of viral process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:RAB7A	involved_in	GO:0019076: viral release from host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:BST2	part_of	GO:0009986: cell surface	ECO:0000315: mutant phenotype evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:BST2	part_of	GO:0005771: multivesicular body	ECO:0000315: mutant phenotype evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:BST2		GO:0005771: multivesicular body	ECO:0000315:		C		Fig. 6D	complete CACAO 3056
HUMAN:BST2		GO:0030139: endocytic vesicle	ECO:0000315:		C		Fig. 6B and Fig. 7B	complete CACAO 3260
HUMAN:BST2		GO:0009986: cell surface	ECO:0000315:		C		Fig. 9	complete CACAO 3261
HUMAN:CD63		GO:0030139: endocytic vesicle	ECO:0000315:		C		Fig. 6B and Fig. 7B	complete CACAO 3259

References

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