title: Rab7A is required for efficient production of infectious HIV-1.
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.
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Caillet
authors.forename: Katy
authors.initials: K
authors.lastname: Janvier
authors.forename: Annegret
authors.initials: A
authors.lastname: Pelchen-Matthews
authors.forename: Delphine
authors.initials: D
authors.lastname: Delcroix-Genête
authors.forename: Grégory
authors.initials: G
authors.lastname: Camus
authors.forename: Mark
authors.initials: M
authors.lastname: Marsh
authors.forename: Clarisse
authors.initials: C
authors.lastname: Berlioz-Torrent
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D011992:Endosomes / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D057074:Virus Release; D054299:env Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D034741:RNA, Small Interfering; D054334:Viral Regulatory and Accessory Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
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