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

EMBO Rep. 2000 Aug;1(2):190-6. doi: 10.1093/embo-reports/kvd025.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / metabolism*
  • Cell Line
  • Cholesterol / metabolism
  • Cyclodextrins / metabolism
  • Cyclodextrins / pharmacology
  • Genes, Reporter
  • HIV Envelope Protein gp120 / metabolism*
  • HIV-1 / metabolism*
  • Humans
  • Membrane Fusion / physiology*
  • Membrane Microdomains / chemistry
  • Membrane Microdomains / drug effects
  • Membrane Microdomains / metabolism*
  • Microscopy, Confocal
  • Protein Binding
  • Receptors, CXCR4 / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • beta-Cyclodextrins*


  • CD4 Antigens
  • Cyclodextrins
  • HIV Envelope Protein gp120
  • Receptors, CXCR4
  • Recombinant Fusion Proteins
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • Cholesterol