Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization
Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization
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DOI：
10.1128/jvi.76.20.10356-10364.2002
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发表时间：
2002-10-01
影响因子：
5.4
通讯作者：
Trono, D
中科院分区：
文献类型：
--
作者：
Guyader, M;Kiyokawa, E;Trono, D
人类免疫缺陷病毒1型(HIV-1)病毒粒子的膜含有高水平的胆固醇和鞘磷脂，这种浓缩是由于病毒通过质膜的RAFT微区优先萌发。当用甲基-β-环糊精去除HIV-1病毒粒子中的胆固醇时，传染性几乎完全消除。相反，这种治疗对水疱性口炎病毒G包膜假型颗粒的感染性只有轻微的影响。胆固醇螯合化合物制霉菌素也有类似的效果。去除胆固醇的HIV-1病毒粒子显示出病毒蛋白的野生型模式，并包含正常水平的亲环素A和糖基磷脂酰肌醇锚定蛋白。然而，尽管它们仍然可以结合靶细胞，但这些病毒粒子在内化方面存在明显缺陷。这些结果表明，存在于HIV-1膜上的胆固醇在融合过程中起着突出的作用，这是病毒进入的关键，并表明能够干扰病毒粒子脂组成的药物可以作为开发杀菌剂的基础。
The membrane of human immunodeficiency virus type 1 (HIV-1) virions contains high levels of cholesterol and sphingomyelin, an enrichment that is explained by the preferential budding of the virus through raft microdomains of the plasma membrane. Upon depletion of cholesterol from HIV-1 virions with methyl-beta-cyclodextrin, infectivity was almost completely abolished. In contrast, this treatment had only a mild effect on the infectiousness of particles pseudotyped with the G envelope of vesicular stomatitis virus. The cholesterol-chelating compound nystatin had a similar effect. Cholesterol-depleted HIV-1 virions exhibited wild-type patterns of viral proteins and contained normal levels of cyclophilin A and glycosylphosphatidylinositol-anchored proteins. Nevertheless, and although they could still bind target cells, these virions were markedly defective for internalization. These results indicate that the cholesterol present in the HIV-1 membrane plays a prominent role in the fusion process that is key to viral entry and suggest that drugs capable of disturbing the lipid composition of virions could serve as a basis for the development of microbicides.