Virion-associated cholesterol is critical for the maintenance of HIV-1 structure and infectivity.
| Autor: | Campbell SM; AIDS Pathogenesis Research Unit, Macfarlane Burnet Institute for Medical Research and Public Health, Prahran, Victoria, Australia., Crowe SM, Mak J |
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| Jazyk: | angličtina |
| Zdroj: | AIDS (London, England) [AIDS] 2002 Nov 22; Vol. 16 (17), pp. 2253-61. |
| DOI: | 10.1097/00002030-200211220-00004 |
| Abstrakt: | 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. (Copyright 2002 Lippincott Williams & Wilkins) |
| Databáze: | MEDLINE |
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