Linked Life Data

13678470

Source:http://linkedlifedata.com/resource/pubmed/id/13678470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2003-9-18
pubmed:abstractText
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-beta-cyclodextrin (beta-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 beta-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. beta-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 beta-cyclodextrin at concentrations that abolished infectivity. Electron microscopy revealed that beta-cyclodextrin-treated HIV had a morphology very similar to that of untreated virus. R18 fluorescence dequenching studies showed that beta-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 beta-cyclodextrin to be an excellent candidate for use as a chemical barrier for AIDS prophylaxis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0889-2229
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
675-87
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells.
pubmed:affiliation
The Leukocyte Immunochemistry Laboratory, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Street, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.