Plasma membrane rafts play a critical role in HIV-1 assembly and release
Plasma membrane rafts play a critical role in HIV-1 assembly and release
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DOI：
10.1073/pnas.241320298
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发表时间：
2001-11-20
影响因子：
11.1
通讯作者：
Freed, EO
中科院分区：
文献类型：
--
作者：
Ono, A;Freed, EO
HIV-1颗粒的产生是在病毒Gag蛋白的推动下进行的一系列步骤。尽管膜的组装和释放发生在质膜上，但膜组装部位的性质仍然知之甚少。我们在这里展示了GAG与质膜上富含胆固醇的微域(“筏”)的特异性结合。动力学研究表明，RAFT结合遵循膜结合，而对Gag突变体的分析表明，虽然Gag的N端介导RAFT结合，但这种结合被Gag-Gag相互作用结构域大大增强。我们观察到，细胞胆固醇的耗尽显著且特别地减少了HIV-1颗粒的产生。此外，用RAFT-干扰剂处理产生病毒的细胞或病毒颗粒会显著降低病毒的感染力。这些结果表明，GAG与质膜筏的联系是HIV-1复制的重要步骤。这些发现可能导致抑制HIV-1在体内复制的新策略。
HIV-1 particle production occurs in a series of steps promoted by the viral Gag protein. Although it is well established that assembly and release take place at the plasma membrane, the nature of membrane assembly sites remains poorly understood. We show here that Gag specifically associates with cholesterol-enriched microdomains ("rafts") at the plasma membrane. Kinetic studies demonstrate that raft association follows membrane binding, and the analysis of Gag mutants reveals that, whereas the N terminus of Gag mediates raft binding, this association is greatly enhanced by Gag-Gag interaction domains. We observe that depletion of cellular cholesterol markedly and specifically reduces HIV-1 particle production. Furthermore, treatment of virus-producing cells or virus particles with raft-disrupting agents significantly impairs virus infectivity. These results identify the association of Gag with plasma membrane rafts as an important step in HIV-1 replication. These findings may lead to novel strategies for suppressing HIV-1 replication in vivo.