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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
被引:47
作者:
Campbell, S
Gaus, K
Bittman, R
Jessup, W
Crowe, S
Mak, J
机构:
[1] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3004, Australia
[2] Monash Univ, Dept Med, Sch Med, Melbourne, Vic 3004, Australia
[3] Natl Ctr HIV Virol Res, Melbourne, Vic, Australia
[4] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia
[5] Univ New S Wales, Sch Med Sci, Ctr Vasc Res, Randwick, NSW, Australia
[6] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3168, Australia
[7] CUNY, Dept Chem & Biochem, Queens Coll, Flushing, NY USA
关键词:
D O I:
10.1128/JVI.78.19.10556-10565.2004
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
摘要:
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.
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页码:10556 / 10565
页数:10
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