HIV entry in macrophages is dependent on intact lipid rafts

被引:107
作者
Carter, Gemma C. [1 ]
Bernstone, Laura [1 ]
Sangani, Dhaval [1 ]
Bee, Jessica Wynter [1 ]
Harder, Thomas [1 ]
James, William [1 ]
机构
[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
基金
英国医学研究理事会;
关键词
HIV; Macrophages; Cholesterol; Entry; Lipid rafts; HUMAN-IMMUNODEFICIENCY-VIRUS; VIRION-ASSOCIATED CHOLESTEROL; MURINE LEUKEMIA-VIRUS; T-CELLS; MEMBRANE MICRODOMAINS; REQUIRES CHOLESTEROL; CHEMOKINE RECEPTORS; CD4; TYPE-1; INFECTION;
D O I
10.1016/j.virol.2008.12.031
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Macrophages are an important natural target cell for HIV-1, but previous studies of virus entry into these cells are limited, and the involvement of membrane cholesterol and lipid rafts is unknown. Cholesterol disruption of macrophage membranes using four pharmacological agents acting by different mechanisms: methyl-beta cyclodextrin, nystatin, filipin complex and Lovastatin, all significantly inhibited productive HIV entry and reverse transcription. The inhibitory effects of these drugs resulted in decreased virus release from infected cells, and could be substantially reversed by the addition of water-soluble cholesterol. The virus bound equally to cholesterol-disrupted cells even though HIV receptor expression levels were significantly reduced. Macrophage CD4 and CCR5 were found to partition with the detergent-resistant membranes with a typical raft-associating protein flotillin-1. HIV particles were observed co-localising with a marker of lipid rafts (CTB-FITC) early post infection. These data suggest that macrophage membrane cholesterol is essential for HIV entry, and implicate lipid raft involvement. (c) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:192 / 202
页数:11
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