Lipid rafts and HIV pathogenesis: Virion-associated cholesterol is required for fusion and infection of susceptible cells

Zhaohao Liao, David R. Graham, James Hildreth

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

We have shown that HIV budding occurs at cholesterol-rich membrane microdomains called lipid rafts (Nguyen and Hildreth, J Virol 2000;74:3264-3272). This observation prompted us to examine the role in HIV entry of cholesterol in the membrane of cells. We recently reported that host cell cholesterol is required for HIV infection (Liao et al., AIDS Res Hum Retroviruses 2001;17:1009-1019). In the present study we examined the role of virion-associated cholesterol in HIV infection by modulating the cholesterol content of virions and infected cells with 2-hydoxypropyl-β-cyclodextrin (β-cyclodextrin). Our results show that removal of cholesterol from the membrane of HIV-infected cells dramatically lowered virus release and that virions released from cholesterol-depleted cells are minimally infectious. Exposure of infectious HIV particles to β-cyclodextrin resulted in a dose-dependent inactivation of the virus. In both cases, the effect was attributable to loss of cholesterol and could be reversed by replenishing cholesterol. β-Cyclodextrin-treated, noninfectious HIV retained its ability to bind cells. Western blot, p24 core ELISA, and reverse transcription assays indicated that virions remained intact after treatment with β-cyclodextrin at concentrations that abolished infectivity. Electron microscopy revealed that β-cyclodextrin-treated HIV had a morphology very similar to that of untreated virus. R18 fluorescence dequenching studies showed that β-cyclodextrin-treated HIV did not fuse to the membrane of susceptible cells. Dequenching was restored by replenishing virion-associated cholesterol. The results indicate that cholesterol in HIV particles is strictly required for fusion and infectivity. These observations in combination with those of past studies indicate β-cyclodextrin to be an excellent candidate for use as a chemical barrier for AIDS prophylaxis.

Original languageEnglish (US)
Pages (from-to)675-687
Number of pages13
JournalAIDS Research and Human Retroviruses
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Virion
Cholesterol
HIV
Cyclodextrins
Lipids
Infection
HIV Infections
Acquired Immunodeficiency Syndrome
Cell Membrane
Membrane Microdomains
Virus Inactivation
Virus Release
Retroviridae
Reverse Transcription
Electron Microscopy
Fluorescence
Western Blotting
Enzyme-Linked Immunosorbent Assay
Viruses
Membranes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Lipid rafts and HIV pathogenesis : Virion-associated cholesterol is required for fusion and infection of susceptible cells. / Liao, Zhaohao; Graham, David R.; Hildreth, James.

In: AIDS Research and Human Retroviruses, Vol. 19, No. 8, 01.08.2003, p. 675-687.

Research output: Contribution to journalArticle

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