Hammache D, Piéroni G, Yahi N, Delézay O, Koch N, Lafont H, Tamalet C, Fantini J
Laboratoire de Biochimie et Biologie de la Nutrition, UPRESA-CNRS 6033, Faculté des Sciences de St Jérôme, 13397 Marseille Cedex 20, France.
J Biol Chem. 1998 Apr 3;273(14):7967-71. doi: 10.1074/jbc.273.14.7967.
Cellular glycosphingolipids mediate the fusion between some viruses and the plasma membrane of target cells. In the present study, we have analyzed the interaction of human immunodeficiency virus (HIV)-1 and HIV-2 surface envelope glycoproteins from distinct viral isolates with monolayers of various glycosphingolipids at the air-water interface. The penetration of the viral glycoproteins into glycosphingolipid monolayers was detected as an increase in the surface pressure. We found that HIV-1 recombinant gp120 (IIIB isolate) could penetrate into a monomolecular film of alpha-hydroxylated galactosylceramide (GalCer-HFA), while ceramides, GluCer, and nonhydroxylated GalCer were totally inactive. The glycoproteins isolated from HIV-1 isolates LAI and NDK and from HIV-2(ROD) could also interact with a GalCer-HFA monolayer, whereas gp120 from HIV-1(SEN) and HIV-1(89.6) did not react. These data correlated with the ability of the corresponding viruses to gain entry into the CD4(-)/GalCer+ cell line HT-29, demonstrating the determinant role of GalCer-HFA in this CD4-independent pathway of HIV-1 and HIV-2 infection. In contrast, all HIV-1 and HIV-2 glycoproteins tested were found to interact with a monolayer of GM3, a ganglioside abundantly expressed in the plasma membrane of CD4(+) lymphocytes and macrophages. A V3 loop-derived synthetic peptide inhibitor of HIV-1 and HIV-2 infection in both CD4(-) and CD4(+) cells could penetrate into various glycosphingolipid monolayers, including GalCer-HFA and GM3. Taken together, these data suggest that the adsorption of human immunodeficiency viruses to the surface of target cells involves an interaction between the V3 domain of the surface envelope glycoprotein and specific glycosphingolipids, i.e. GalCer-HFA for CD4(-) cells and GM3 for CD4(+) cells.
细胞糖鞘脂介导某些病毒与靶细胞质膜之间的融合。在本研究中，我们分析了来自不同病毒分离株的人类免疫缺陷病毒（HIV）-1和HIV-2表面包膜糖蛋白与气-水界面处各种糖鞘脂单层的相互作用。病毒糖蛋白渗透到糖鞘脂单层中表现为表面压力增加。我们发现HIV-1重组gp120（IIIB分离株）能够渗透到α-羟基化半乳糖神经酰胺（GalCer-HFA）的单分子膜中，而神经酰胺、葡糖神经酰胺和非羟基化GalCer则完全无活性。从HIV-1分离株LAI和NDK以及HIV-2（ROD）中分离出的糖蛋白也能与GalCer-HFA单层相互作用，而来自HIV-1（SEN）和HIV-1（89.6）的gp120则无反应。这些数据与相应病毒进入CD4（-）/GalCer +细胞系HT-29的能力相关，证明了GalCer-HFA在HIV-1和HIV-2这种不依赖CD4的感染途径中的决定性作用。相反，所有测试的HIV-1和HIV-2糖蛋白都被发现能与GM3单层相互作用，GM3是一种在CD4（+）淋巴细胞和巨噬细胞质膜中大量表达的神经节苷脂。一种在CD4（-）和CD4（+）细胞中均能抑制HIV-1和HIV-2感染的V3环衍生合成肽抑制剂能够渗透到各种糖鞘脂单层中，包括GalCer-HFA和GM3。综上所述，这些数据表明人类免疫缺陷病毒吸附到靶细胞表面涉及表面包膜糖蛋白的V3结构域与特定糖鞘脂之间的相互作用，即对于CD4（-）细胞是GalCer-HFA，对于CD4（+）细胞是GM3。
