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Journal of Virology, October 2002, p. 10356-10364, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10356-10364.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Role for Human Immunodeficiency Virus Type 1 Membrane Cholesterol in Viral Internalization

Mireille Guyader, Etsuko Kiyokawa,{dagger} Laurence Abrami, Priscilla Turelli, and Didier Trono*

Department of Genetics and Microbiology, University of Geneva, Geneva, Switzerland

Received 26 December 2001/ Accepted 3 July 2002

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-ß-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.

* Corresponding author. Mailing address: Department of Genetics and Microbiology, C. M. U., 1, rue Michel-Servet, 1211 Geneva 4, Switzerland. Phone: (41 22) 702 5720. Fax: (41 22) 702 5721. E-mail: didier.trono{at}medecine.unige.ch.

{dagger} Present address: Sphingolipid Functions Laboratory, Supra-Biomolecular System Research Group, RIKEN Frontier Research System, Saitama, Japan.

Journal of Virology, October 2002, p. 10356-10364, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10356-10364.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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