Zheng Y H, Plemenitas A, Linnemann T, Fackler O T, Peterlin B M
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Curr Biol. 2001 Jun 5;11(11):875-9. doi: 10.1016/s0960-9822(01)00237-8.
Lipid rafts, also known as detergent-resistant membranes (DRM), are microdomains in the plasma membrane enriched in sphingolipids and cholesterol (reviewed in [1, 2]). Human immunodeficiency virus 1 (HIV) buds via lipid rafts [3, 4]. However, the targeting of viral structural components to DRM and its consequences for viral replication are not understood. Moreover, the negative factor Nef from HIV increases viral infectivity (reviewed in [5, 6]). With no apparent differences in structural components and morphology between wild-type and DeltaNef virons, the latter viruses display less efficient reverse transcription in target cells. As Nef is expressed abundantly early in the viral replicative cycle [7], we hypothesized that Nef could affect viral morphogenesis and budding to render viruses more infectious. In this report, we demonstrated first that Nef increases viral budding from lipid rafts. Second, in the presence of Nef, viral envelopes contain more ganglioside (GM1), which is a major component of lipid rafts. This finding correlated directly with the increased infectivity of HIV. Finally, the depletion of exogenous and endogenous cholesterol biochemically and genetically, which disrupted lipid rafts, decreased viral infectivity only in the presence of Nef. Importantly, HIV lacking the nef gene remained unaffected by these manipulations. We conclude that lipids in virions are essential for viral infectivity. Thus, HIV becomes more infectious when it buds from lipid rafts, and Nef plays a major role in this process.
脂筏，也称为抗去污剂膜（DRM），是质膜中富含鞘脂和胆固醇的微结构域（见[1,2]综述）。人类免疫缺陷病毒1型（HIV）通过脂筏出芽[3,4]。然而，病毒结构成分靶向DRM及其对病毒复制的影响尚不清楚。此外，HIV的负调控因子Nef可增加病毒感染性（见[5,6]综述）。野生型和缺失Nef的病毒体在结构成分和形态上没有明显差异，但后者在靶细胞中的逆转录效率较低。由于Nef在病毒复制周期早期大量表达[7]，我们推测Nef可能影响病毒形态发生和出芽，使病毒更具感染性。在本报告中，我们首先证明Nef增加了病毒从脂筏出芽。其次，在有Nef存在的情况下，病毒包膜含有更多的神经节苷脂（GM1），这是脂筏的主要成分。这一发现与HIV感染性增加直接相关。最后，通过生化和基因手段消耗外源性和内源性胆固醇，破坏了脂筏，仅在有Nef存在时降低了病毒感染性。重要的是，缺乏nef基因的HIV不受这些操作的影响。我们得出结论，病毒体中的脂质对病毒感染性至关重要。因此，HIV从脂筏出芽时更具感染性，而Nef在这一过程中起主要作用。
