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Rab7A is required for efficient production of infectious HIV-1.
Caillet M., Janvier K., Pelchen-matthews A., Delcroix-Genête D., Camus G., Marsh M., Berlioz-Torrent C.
PLoS Pathogens 7, 11 (2011) e1002347 - http://www.hal.inserm.fr/inserm-00693726
 (22072966) 
Rab7A is required for efficient production of infectious HIV-1.
Marina Caillet1, Katy Janvier1, Annegret Pelchen-matthews2, Delphine Delcroix-Genête1, Gregory Camus1, Mark Marsh2, Clarisse Berlioz-Torrent () 1, Mark Marsh Collaboration(s)
1 :  Institut Cochin
INSERM : U1016 – CNRS : UMR8104 – Université Paris V - Paris Descartes
22 rue Méchain, 75014 Paris
France
2 :  Cell Biology Unit
MRC Laboratory for Molecular Cell Biology – University College London
London
Royaume-Uni
3 - Cell Biology Unit, MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
Rab7A and Production of Infectious HIV Particles
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.
Sciences du Vivant/Médecine humaine et pathologie/Maladies infectieuses
Anglais
1553-7366

Articles dans des revues avec comité de lecture
10.1371/journal.ppat.1002347
PLoS Pathogens
Publisher Public Library of Science
ISSN 1553-7366 (eISSN : 1553-7374)
internationale
11/2011
03/11/2011
7
11
e1002347

M.C holds a fellowship from the ''Ministe're franc¸ais de l'enseignement supe'rieur et de la Recherche'' and a fellowship from SIDACTION. G.C. holds a fellowship from ANRS. AP-M and MM were supported by UK Medical Research Council funding to the MRC Cell Biology Unit. This work is funded by ANRS, the ANR-07-JCJC-0102 program and is part of the activities of the HIV-ACE research network (HEALTH-F3-2008-201095) supported by a grant of the European Commission, within the Priority 1 ''Health'' work programme of the 7th Framework Programme of the EU.
Référence du projet ANR-07-JCJC-0102
Année 2007
Acronyme du projet JCJC
Titre du projet Cellular cofactors of the HIV-1 Gag and Env proteins involved in the late steps of the HIV-1 replicative cycle.
Intitulé Jeunes chercheuses & jeunes chercheurs
Acronyme de l'appel JC - CBT
Numéro Cordis 201095
Acronyme HIV ACE
Titre Targeting assembly of infectious HIV particles
Financé par HEALTH
Début 2008-03-01
Date de fin 2011-08-31
Identifiant de l'appel FP7-HEALTH-2007-A
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journal.ppat.1002347.pdf(7.5 MB)

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