Membrane raft microdomains mediate lateral assemblies required for HIV-1 infection

TitleMembrane raft microdomains mediate lateral assemblies required for HIV-1 infection
Publication TypeJournal Article
Year of Publication2000
AuthorsManes, S, Del Real G, Lacalle RA, Lucas P, Gomez-Mouton C, Sanchez-Palomino S, Delgado R, Alcami J, Mira E, Martinez AC
JournalEMBO Rep
Volume1
Pagination190-6
Date PublishedAug
ISBN Number1469-221X (Print)1469-221X (Linking)
Accession Number11265761
Keywords*beta-Cyclodextrins, Animals, Antigens, CD4/*metabolism, Cell Line, Cholesterol/metabolism, Cyclodextrins/metabolism/pharmacology, Genes, Reporter, HIV Envelope Protein gp120/*metabolism, HIV-1/*metabolism, Humans, Membrane Fusion/*physiology, Membrane Microdomains/chemistry/drug effects/*metabolism, Microscopy, Confocal, Protein Binding, Receptors, CXCR4/*metabolism, Recombinant Fusion Proteins/genetics/metabolism
Abstract

HIV-1 infection triggers lateral membrane diffusion following interaction of the viral envelope with cell surface receptors. We show that these membrane changes are necessary for infection, as initial gp120-CD4 engagement leads to redistribution and clustering of membrane microdomains, enabling subsequent interaction of this complex with HIV-1 co-receptors. Disruption of cell membrane rafts by cholesterol depletion before viral exposure inhibits entry by both X4 and R5 strains of HIV-1, although viral replication in infected cells is unaffected by this treatment. This inhibitory effect is fully reversed by cholesterol replenishment of the cell membrane. These results indicate a general mechanism for HIV-1 envelope glycoprotein-mediated fusion by reorganization of membrane microdomains in the target cell, and offer new strategies for preventing HIV-1 infection.

URLhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11265761