title: Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization.
abstract: The membrane of human immunodeficiency virus type 1 (HIV-1) virions contains high levels of cholesterol and sphingomyelin, an enrichment that is explained by the preferential budding of the virus through raft microdomains of the plasma membrane. Upon depletion of cholesterol from HIV-1 virions with methyl-beta-cyclodextrin, infectivity was almost completely abolished. In contrast, this treatment had only a mild effect on the infectiousness of particles pseudotyped with the G envelope of vesicular stomatitis virus. The cholesterol-chelating compound nystatin had a similar effect. Cholesterol-depleted HIV-1 virions exhibited wild-type patterns of viral proteins and contained normal levels of cyclophilin A and glycosylphosphatidylinositol-anchored proteins. Nevertheless, and although they could still bind target cells, these virions were markedly defective for internalization. These results indicate that the cholesterol present in the HIV-1 membrane plays a prominent role in the fusion process that is key to viral entry and suggest that drugs capable of disturbing the lipid composition of virions could serve as a basis for the development of microbicides.
authors.affiliation: Department of Genetics and Microbiology, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.
authors.forename: Mireille
authors.initials: M
authors.lastname: Guyader
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kiyokawa
authors.forename: Laurence
authors.initials: L
authors.lastname: Abrami
authors.forename: Priscilla
authors.initials: P
authors.lastname: Turelli
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
mesh_terms: D002784:Cholesterol / Q000378:metabolism / Q000502:physiology*; D004705:Endocytosis; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D014764:Viral Proteins / Q000032:analysis; D014771:Virion / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D002784:Cholesterol