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AIDS. 2002 Nov 22;16(17):2253-61.

Virion-associated cholesterol is critical for the maintenance of HIV-1 structure and infectivity.

Author information

1
AIDS Pathogenesis Research Unit, Macfarlane Burnet Institute for Medical Research and Public Health, Prahran, Victoria, Australia.

Abstract

OBJECTIVE:

HIV-1 particles are enriched with cholesterol; however, the significance of this cholesterol enrichment is unknown. This study examines the structural and functional roles of cholesterol in HIV-1 replication.

METHODS:

Using methyl-beta-cyclodextrin (CD) to remove cholesterol from the HIV-1 envelope, buoyant density and infectivity of the cholesterol-deficient HIV-1 particles were compared with the untreated control. The specificity and requirement of cholesterol as an HIV-1-associated lipid were investigated by replenishing cholesterol-deficient HIV-1 with cholesterol, cholestenone (a cholesterol structural analogue) or sphingomyelin (a structurally unrelated yet virion-associated lipid).

RESULTS:

CD-mediated removal of virion cholesterol increased the buoyant density of virion particles and reduced HIV-1 infectivity. Trans-supplementation of exogenous cholesterol rescued the defects associated with CD-induced cholesterol depletion in HIV-1. However, the restoration of viral infectivity could not be achieved by trans-supplementation of either cholestenone or sphingomyelin.

CONCLUSION:

This study provides the first direct evidence that HIV-1-associated cholesterol is important for the maintenance of virion structure and infectivity. While the buoyant density of cholesterol-defective HIV-1 can be restored by a cholesterol structural analogue, cholestenone, the requirement for cholesterol is essential for HIV-1 infectivity.

[Indexed for MEDLINE]

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