title: HIV entry in macrophages is dependent on intact lipid rafts.
abstract: 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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Carter
authors.forename: Laura
authors.initials: L
authors.lastname: Bernstone
authors.forename: Dhaval
authors.initials: D
authors.lastname: Sangani
authors.forename: Jessica Wynter
authors.initials: JW
authors.lastname: Bee
authors.forename: Thomas
authors.initials: T
authors.lastname: Harder
authors.forename: William
authors.initials: W
authors.lastname: James
mesh_terms: D000963:Antimetabolites / Q000494:pharmacology; D002478:Cells, Cultured; D005372:Filipin / Q000494:pharmacology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D009761:Nystatin / Q000494:pharmacology; D053585:Virus Attachment; D053586:Virus Internalization; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D009761:Nystatin; D005372:Filipin; D008148:Lovastatin