title: Properties of HIV-1 associated cholesterol in addition to raft formation are important for virus infection.
abstract: The overall HIV-1 membrane lipid contents resemble lipid rafts, and we have previously demonstrated that raft-promoting properties of virus-associated cholesterol (with modifications in either the 3β-OH group or AB rings) are important for HIV-1 infectivity. As cholesterol is present in both rafts and non-rafts domains of HIV-1 membrane, we question whether the interpretation of rafts property of virus-associated cholesterol being an absolute requirement for HIV-1 function is too simplistic. The carbon side chain of cholesterol is the third component of cholesterol that can affect the fluidity of membrane depending on its context within the lipid membrane bilayers. In this work, we have used synthetic cholesterol analogues that have different lengths of carbon side chain for our investigation. In contrast to our previous report, we have found that cholesterol side chain analogues that lack in vitro defined raft promoting-property is able to support HIV-1 replication. More specifically, cholesterol analogues with side chains of intermediate length have greater capacity to support HIV-1 infection, suggesting HIV-1 is able to maintain function using cholesterol variants that promote a range of non-rafts- to rafts-properties. Our data demonstrate cholesterol properties other than raft-promoting function also contribute to the infectivity of HIV-1.
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Hawkes
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Jones
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Redmond P
authors.initials: RP
authors.lastname: Smyth
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Cândida F
authors.initials: CF
authors.lastname: Pereira
authors.affiliation: Queens College of City University of New York, Flushing, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Jaworowski
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia; Deakin University, Victoria, Australia; CSIRO AAHL, Victoria, Australia. Electronic address: johnson.mak@deakin.edu.au.
authors.forename: Johnson
authors.initials: J
authors.lastname: Mak
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D053586:Virus Internalization
chemical_list: D002784:Cholesterol
keywords: Cholesterol; HIV; Lipid rafts; Viral entry; Virion membrane