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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

Campbell, Shahan, Gaus, Katharina, Bittman, Robert, Jessup, Wendy, Crowe, Suzanne and Mak, Johnson 2004, 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, Journal of virology, vol. 78, no. 19, pp. 10556-10565, doi: 10.1128/JVI.78.19.10556-10565.2004.

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Title 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
Author(s) Campbell, Shahan
Gaus, Katharina
Bittman, Robert
Jessup, Wendy
Crowe, Suzanne
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Journal name Journal of virology
Volume number 78
Issue number 19
Start page 10556
End page 10565
Total pages 10
Publisher American Society for Microbiology
Place of publication Washington, D. C.
Publication date 2004-10
ISSN 0022-538X
1098-5514
Keyword(s) centrifugation
density gradient
cholesterol
HIV-1
humans
immunoblotting
lipids
membrane lipids
membrane microdomains
octoxynol
plant oils
polyethylene glycols
viral proteins
virion
virus replication
Summary 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.
Language eng
DOI 10.1128/JVI.78.19.10556-10565.2004
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2004, American Society for Microbiology
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047540

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.