title: Self assembly of HIV-1 Gag protein on lipid membranes generates PI(4,5)P2/Cholesterol nanoclusters.
abstract: The self-assembly of HIV-1 Gag polyprotein at the inner leaflet of the cell host plasma membrane is the key orchestrator of virus assembly. The binding between Gag and the plasma membrane is mediated by specific interaction of the Gag matrix domain and the PI(4,5)P2lipid (PIP2). It is unknown whether this interaction could lead to local reorganization of the plasma membrane lipids. In this study, using model membranes, we examined the ability of Gag to segregate specific lipids upon self-assembly. We show for the first time that Gag self-assembly is responsible for the formation of PIP2lipid nanoclusters, enriched in cholesterol but not in sphingomyelin. We also show that Gag mainly partition into liquid-disordered domains of these lipid membranes. Our work strongly suggests that, instead of targeting pre-existing plasma membrane lipid domains, Gag is more prone to generate PIP2/Cholesterol lipid nanodomains at the inner leaflet of the plasma membrane during early events of virus assembly.
authors.affiliation: CNRS-Université Montpellier, Centre d'études d'agents Pathogenes et de Biotechnologies pour la Santé, Montpellier, France.
authors.forename: Naresh
authors.initials: N
authors.lastname: Yandrapalli
authors.affiliation: CNRS-Université Grenoble, Institut National de Physique, Grenoble, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Lubart
authors.affiliation: Deakin University, School of Medicine, Melbourne, Australia.
authors.forename: Hanumant S
authors.initials: HS
authors.lastname: Tanwar
authors.affiliation: CNRS-Université Grenoble, Institut National de Physique, Grenoble, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Picart
authors.affiliation: Deakin University, School of Medicine, Melbourne, Australia.
authors.forename: Johnson
authors.initials: J
authors.lastname: Mak
authors.affiliation: CNRS-Université Montpellier, Centre d'études d'agents Pathogenes et de Biotechnologies pour la Santé, Montpellier, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Muriaux
authors.affiliation: CNRS-Université Montpellier, Centre d'études d'agents Pathogenes et de Biotechnologies pour la Santé, Montpellier, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Favard
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D008051:Lipid Bilayers / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D019269:Phosphatidylinositol 4,5-Diphosphate; D054301:gag Gene Products, Human Immunodeficiency Virus; D002784:Cholesterol