Fantini J, Hammache D, Piéroni G, Yahi N
Laboratoire de Biochimie et Biologie de la Nutrition, ESA-CNRS 6033, Faculté des Sciences de St Jérome, Marseille, France.
Glycoconj J. 2000 Mar-Apr;17(3 -4):199-204. doi: 10.1023/a:1026537122903.
The fusion of HIV-1 with the plasma membrane of CD4+ cells is triggered by the interaction of HIV-1 surface envelope glycoprotein gp120 with the CD4 receptor, and requires coreceptors (CCR5 and CXCR4). Recent advances in the study of HIV-1 entry into CD4+ cells suggest that glycosphingolipids (GSL) may also participate in the fusion process. GSL are organized in functional microdomains which are associated with specific membrane proteins such as CD4. GSL-enriched microdomains were purified from human lymphocytes and reconstituted as a monomolecular film at the air-water interface of a Langmuir film balance. Surface pressure measurements allowed to characterize the sequential interaction of GSL with CD4 and with gp120. Using this approach, we identified globotriaosylceramide (Gb3) and ganglioside GM3 as the main lymphocyte GSL recognized by gp120. In both cases, the interaction was saturable and dramatically increased by CD4. We propose that GSL microdomains behave as moving platforms allowing the recruitment of HIV-1 coreceptors after the initial interaction between the viral particle and CD4. According to this model, the GSL microdomain may: i) stabilize the attachment of the virus with the cell surface through multiple low affinity interactions between the V3 domain of gp120 and the carbohydrate moiety of GSL, and ii) convey the virus to an appropriate coreceptor by moving freely in the outer leaflet of the plasma membrane. This model can be extrapolated to all envelope viruses (e.g. influenza virus) that use cell surface GSL of the host cells as receptors or coreceptors.
HIV-1与CD4+细胞的质膜融合是由HIV-1表面包膜糖蛋白gp120与CD4受体相互作用触发的，并且需要共受体（CCR5和CXCR4）。关于HIV-1进入CD4+细胞的研究的最新进展表明，糖鞘脂（GSL）也可能参与融合过程。GSL在与特定膜蛋白（如CD4）相关的功能微结构域中组织。从人淋巴细胞中纯化富含GSL的微结构域，并在Langmuir膜天平的气-水界面重构为单分子膜。表面压力测量能够表征GSL与CD4以及与gp120的顺序相互作用。使用这种方法，我们确定了球三糖神经酰胺（Gb3）和神经节苷脂GM3是被gp120识别的主要淋巴细胞GSL。在这两种情况下，相互作用都是可饱和的，并且被CD4显著增强。我们提出，GSL微结构域充当移动平台，在病毒颗粒与CD4最初相互作用后允许募集HIV-1共受体。根据这个模型，GSL微结构域可能：i）通过gp120的V3结构域与GSL的碳水化合物部分之间的多个低亲和力相互作用稳定病毒与细胞表面的附着，以及ii）通过在质膜外小叶中自由移动将病毒传递到合适的共受体。该模型可以外推到所有利用宿主细胞的细胞表面GSL作为受体或共受体的包膜病毒（如流感病毒）。
