Hammar L, Hirsch I, Machado A A, De Mareuil J, Baillon J G, Bolmont C, Chermann J C
Department of Dermatology, Karolinska Institute, Stockholm, Sweden.
AIDS Res Hum Retroviruses. 1995 Jan;11(1):87-95. doi: 10.1089/aid.1995.11.87.
Lectins with specificity for terminal mannose residues and anti-mannan antibodies neutralize HIV-1 infection in vitro. This is assumed to be caused by binding of the agents to the viral glycoproteins. In this study we show that one such agent, the Galanthus nivalis lectin (GNA), also blocks infection at the target cell level. To explore the effect of GNA on HIV infection we used the two HIV-1 isolates LAV and NDK, representing in the first case a prototype virus and in the latter case a highly cytopathic virus, which spreads preferentially via cell-to-cell contact. MT-4 cells were used as target cells and infection was determined from the occurrence of syncytia. Cell-to-cell infection was studied with CEM cells persistently infected with the two virus isolates. GNA, at concentrations in the nanogram per milliliter range, neutralized the HIV-1 isolates LAV, NDK, and MN as well as HIV-2ROD. Pretreatment of cells with the lectin, before addition of virus, or of infected cells, also blocked infection. This effect was more pronounced with HIV-1NDK than with HIV-1LAV. Mannosidase treatment of the target cells abolished the GNA effect on HIV-1NDK infection. It is concluded that GNA inhibits infection of several HIV isolates. It neutralizes infection by binding to the virion but also blocks infection at the target cell level. The latter effect may be different for different virus isolates. Mannosyl residuals at the cell surface are targets for GNA modulation of infection with the cytopathic HIV-1NDK. These do not represent essential virus receptors.
对末端甘露糖残基具有特异性的凝集素和抗甘露聚糖抗体可在体外中和HIV-1感染。据推测,这是由于这些试剂与病毒糖蛋白结合所致。在本研究中,我们表明,一种这样的试剂,即雪花莲凝集素(GNA),也在靶细胞水平阻断感染。为了探索GNA对HIV感染的影响,我们使用了两种HIV-1分离株LAV和NDK,前者代表原型病毒,后者代表高度致细胞病变的病毒,其优先通过细胞间接触传播。MT-4细胞用作靶细胞,通过合胞体的出现来确定感染情况。用持续感染这两种病毒分离株的CEM细胞研究细胞间感染。GNA在每毫升纳克浓度范围内可中和HIV-1分离株LAV、NDK和MN以及HIV-2 ROD。在加入病毒之前用凝集素预处理细胞,或对感染细胞进行预处理,也可阻断感染。这种效应在HIV-1 NDK中比在HIV-1 LAV中更明显。对靶细胞进行甘露糖苷酶处理消除了GNA对HIV-1 NDK感染的影响。得出的结论是,GNA抑制几种HIV分离株的感染。它通过与病毒粒子结合来中和感染,但也在靶细胞水平阻断感染。后一种效应可能因不同的病毒分离株而异。细胞表面的甘露糖残基是GNA调节细胞病变性HIV-1 NDK感染的靶点。这些并不代表必需的病毒受体。