Depletion of cellular cholesterol inhibits membrane binding and higher-order multimerization of human immunodeficiency virus type 1 Gag
Depletion of cellular cholesterol inhibits membrane binding and higher-order multimerization of human immunodeficiency virus type 1 Gag
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DOI：
10.1016/j.virol.2006.10.011
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发表时间：
2007-03-30
期刊：
影响因子：
3.7
通讯作者：
Freed, Eric O.
中科院分区：
文献类型：
--
作者：
Ono, Akira;Waheed, Abdul A.;Freed, Eric O.
最近的研究表明，质膜含有富含胆固醇的微区，称为脂筏。HIV-1 Gag结合质膜的筏状丰富区域，胆固醇描绘损害HIV-1颗粒的产生。在这项研究中，我们试图确定胆固醇消耗所造成的阻滞。我们观察到，膜结合和高阶多聚化的Gag显着降低胆固醇耗竭。将高效的异源膜结合序列与Gag融合，逆转了由胆固醇描绘引起的Gag-膜结合和多聚化的缺陷，表明可以通过增加Gag对膜的亲和力来规避降低膜胆固醇含量对Gag-膜结合和多聚化的影响。这种Gag衍生物的病毒释放效率受胆固醇消耗的影响最小。总之，这些结果与以下假设一致：富含胆固醇的膜微区通过促进Gag-膜结合和Gag多聚化促进HIV-1颗粒产生。(c)2006年爱思唯尔公司All rights reserved.
Recent studies have suggested that the plasma membrane contains cholesterol-enriched microdomains known as lipid rafts. HIV-1 Gag binds raft-rich regions of the plasma membrane, and cholesterol depiction impairs HIV-1 particle production. In this study, we sought to define the block imposed by cholesterol depletion. We observed that membrane binding and higher-order multimerization of Gag were markedly reduced upon cholesterol depletion. Fusing to Gag a highly efficient, heterologous membrane-binding sequence reversed the defects in Gag-membrane binding and multimerization caused by cholesterol depiction, indicating that the impact of reducing the membrane cholesterol content on Gag-membrane binding and multimerization can be circumvented by increasing the affinity of Gag for membrane. Virus release efficiency of this Gag derivative was minimally affected by cholesterol depletion. Altogether, these results are consistent with the hypothesis that cholesterol-enriched membrane microdomains promote HIV-1 particle production by facilitating both Gag-membrane binding and Gag multimerization. (c) 2006 Elsevier Inc. All rights reserved.