Profile of resistance of human immunodeficiency virus to mannose-specific plant lectins
Profile of resistance of human immunodeficiency virus to mannose-specific plant lectins
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DOI：
10.1128/jvi.78.19.10617-10627.2004
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Schols, D
中科院分区：
文献类型：
--
作者：
Balzarini, J;Van Laethem, K;Schols, D
来自Amaryllidaceae家族的甘露糖特异性植物凝集素（例如Hippeastrumsp。Hybrid和Galanthus nivalis）抑制人类免疫缺陷病毒（HIV）人类淋巴细胞感染的人类淋巴细胞感染，细胞在每毫升范围内较高的纳米含量和抑制Syncium formistium consymtium formist parsissississississississississississississississississississississississississississississississississississississississississississississississississississississississises， （HIV-1）感染的细胞和未感染的细胞CD4（+）T细胞。这些凝集素抑制了病毒的进入。当暴露于G. nivalis和Hippeastrum sp。混合凝集素，在20至40个亚培养后分离出多种HIV-1（IIIB）菌株，这些菌株对植物凝集素的敏感性降低。观察到突变病毒分离株的包膜糖蛋白GP120的几种氨基酸变化。绝大多数氨基酸的变化发生在N糖基化位点以及属于N糖基化基序的S或T残基上。对植物凝集素的耐药性与GP120中突变的糖基化位点的数量不断相关。这些突变的性质与在其他病毒进入抑制剂（如硫酸葡萄酸盐，自行车，自行车）（即AMD3100）和奇罗酸等其他病毒抑制剂的压力下已知出现在HIV-1 GP120中的突变的性质完全不同，这也解释了缺乏针对任何其他HIV抑制剂（包括T-20和蓝绿色藻类）的植物耐药病毒的交叉抗性（蓝细菌）衍生的甘露糖特异性蓝藻。植物凝集素代表了一种定义明确的抗HIV（微生物）药物，其新型HIV耐药性概况与其他现有抗HIV药物不同。
The mannose-specific plant lectins from the Amaryllidaceae family (e.g., Hippeastrum sp. hybrid and Galanthus nivalis) inhibit human immunodeficiency virus (HIV) infection of human lymphocytic, cells in the higher nanogram per milliliter range and suppress syncytium formation between persistently HIV type 1 (HIV-1)-infected cells and uninfected CD4(+) T cells. These lectins inhibit virus entry. When exposed to escalating concentrations of G. nivalis and Hippeastrum sp. hybrid agglutinin, a variety of HIV-1 (IIIB) strains were isolated after 20 to 40 subcultivations which showed a decreased sensitivity to the plant lectins. Several amino acid changes in the envelope glycoprotein gp120, but not in gp41, of the mutant virus isolates were observed. The vast majority of the amino acid changes occurred at the N glycosylation sites and at the S or T residues that are part of the N glycosylation motif. The degree of resistance to the plant lectins was invariably correlated with an increasing number of mutated glycosylation sites in gp120. The nature of these mutations was entirely different from that of mutations that are known to appear in HIV-1 gp120 under the pressure of other viral entry inhibitors such as dextran sulfate, bicyclams (i.e., AMD3100), and chicoric acid, which also explains the lack of cross-resistance of plant lectin-resistant viruses to any other HIV inhibitor including T-20 and the blue-green algae (cyanobacteria)-derived mannose-specific cyanovirin. The plant lectins represent a well-defined class of anti-HIV (microbicidal) drugs with a novel HIV drug resistance profile different from those of other existing anti-HIV drugs.