Marked depletion of glycosylation sites in HIV-1 gp120 under selection pressure by the mannose-specific plant lectins of Hippeastrum hybrid and Galanthus nivalis
Marked depletion of glycosylation sites in HIV-1 gp120 under selection pressure by the mannose-specific plant lectins of Hippeastrum hybrid and Galanthus nivalis
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DOI：
10.1124/mol.104.005082
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发表时间：
2005-05-01
影响因子：
3.6
通讯作者：
Schols, D
中科院分区：
文献类型：
--
作者：
Balzarini, J;Van Laethem, K;Schols, D
朱顶红和雪花莲的植物凝集素是50，000-D四聚体，对α-（1，3）和/或α-（1，6）-甘露糖低聚物具有特异性。它们在0.2至0.3 μ g/ ml的50%有效浓度下抑制HIV-1感染。HHA或GNA浓度升高（高达500 μ g/ ml）导致在CEM T细胞培养物中分离出三种HIV-1（III B）菌株，它们对HHA和GNA、几种其它相关的甘露糖特异性植物凝集素和单克隆抗体2G 12具有高度抗性，单克隆抗体2G 12对甘露糖特异性氰核苷酸具有中度抗性，氰核苷酸来源于蓝绿色甜菜碱，但对其他HIV进入抑制剂以及HIV逆转录酶抑制剂完全敏感。由于N-糖基化基序的Asn或Thr/Ser位点的突变，这些突变病毒株缺乏病毒包膜糖蛋白gp 120中22个糖基化位点中的多达7个或8个。在其中一个菌株中，在缺失的糖基化位点附近产生了新的糖基化位点。受影响的糖基化位点主要聚集在gp 120的区域中，这些区域不参与与CD 4、CCR 5、CXCR 4或gp 41的直接相互作用。含有糖基化位点缺失的突变病毒在CEM T细胞培养物中的感染性明显高于野生型病毒。
The plant lectins from Hippeastrum hybrid (HHA) and Galanthus nivalis (GNA) are 50,000-D tetramers showing specificity for alpha-( 1,3) and/or alpha-(1,6)-mannose oligomers. They inhibit HIV-1 infection at a 50% effective concentration of 0.2 to 0.3 mu g/ ml. Escalating HHA or GNA concentrations ( up to 500 mu g/ ml) led to the isolation of three HIV-1(III B) strains in CEM T cell cultures that were highly resistant to HHA and GNA, several other related mannose-specific plant lectins, and the monoclonal antibody 2G12, modestly resistant to the mannose-specific cyanovirin, which is derived from a blue-green alga, but fully susceptible to other HIV entry inhibitors as well as HIV reverse transcriptase inhibitors. These mutant virus strains were devoid of up to seven or eight of 22 glycosylation sites in the viral envelope glycoprotein gp120 because of mutations at the Asn or Thr/Ser sites of the N-glycosylation motifs. In one of the strains, a novel glycosylation site was created near a deleted glycosylation site. The affected glycosylation sites were predominantly clustered in regions of gp120 that are not involved in the direct interaction with either CD4, CCR5, CXCR4, or gp41. The mutant viruses containing the deleted glycosylation sites were markedly more infectious in CEM T-cell cultures than wild-type virus.