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Journal of Virology, October 2004, p. 10556-10565, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10556-10565.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Raft-Promoting Property of Virion-Associated Cholesterol, but Not the Presence of Virion-Associated Brij 98 Rafts, Is a Determinant of Human Immunodeficiency Virus Type 1 Infectivity

Shahan Campbell,1,2 Katharina Gaus,3 Robert Bittman,4 Wendy Jessup,3 Suzanne Crowe,1,5,6 and Johnson Mak1,7*

Macfarlane Burnet Institute for Medical Research and Public Health,1 Department of Medicine, Monash Medical School, Monash University,5 National Centre for HIV Virology Research, Melbourne,6 Department of Microbiology and Immunology, University of Melbourne, Parkville,2 Centre for Vascular Research, School of Medical Science, University of New South Wales, Randwick,3 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia,7 Department of Chemistry and Biochemistry, Queens College, City University of New York, Flushing, New York4

Received 11 March 2004/ Accepted 5 June 2004

Lipid rafts are enriched in cholesterol and sphingomyelin and are isolated on the basis of insolubility in detergents, such as Brij 98 and Triton X-100. Recent work by Holm et al. has shown that rafts insoluble in Brig 98 can be found in human immunodeficiency virus type 1 (HIV-1) virus-like particles, although it is not known whether raft-like structures are present in authentic HIV-1 and it is unclear whether a virion-associated raft-like structure is required for HIV replication. Independently, it was previously reported that virion-associated cholesterol is critical for HIV-1 infectivity, although the specific requirement of virion cholesterol in HIV-1 was not examined. In the present study, we have demonstrated that infectious wild-type HIV-1 contains Brij 98 rafts but only minimal amounts of Triton X-100 rafts. To directly assess the functional requirement of virion-associated rafts and various features of cholesterol on HIV-1 replication, we replaced virion cholesterol with exogenous cholesterol analogues that have demonstrated either raft-promoting or -inhibiting capacity in model membranes. We observed that variable concentrations of exogenous analogues are required to replace a defined amount of virion-associated cholesterol, showing that structurally diverse cholesterol analogues have various affinities toward HIV-1. We found that replacement of 50% of virion cholesterol with these exogenous cholesterol analogues did not eliminate the presence of Brij 98 rafts in HIV-1. However, the infectivity levels of the lipid-modified HIV-1s directly correlate with the raft-promoting capacities of these cholesterol analogues. Our data provide the first direct assessment of virion-associated Brij 98 rafts in retroviral replication and illustrate the importance of the raft-promoting property of virion-associated cholesterol in HIV-1 replication.

* Corresponding author. Mailing address: Macfarlane Burnet Institute for Medical Research and Public Health, Cnr Punt and Commercial Roads, Melbourne 3004, Victoria, Australia. Phone: 61 (3) 9282 2217. Fax: 61 (3) 9282 2142. E-mail: mak{at}burnet.edu.au.

Journal of Virology, October 2004, p. 10556-10565, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10556-10565.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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