对抗人免疫缺陷病毒1型化合物L-菊苣酸的耐药性是由整合酶第140位氨基酸的单一突变引起的。
Resistance to the anti-human immunodeficiency virus type 1 compound L-chicoric acid results from a single mutation at amino acid 140 of integrase.
作者信息
King P J, Robinson W E
机构信息
Departments of Microbiology and Molecular Genetics, University of California, Irvine, California 92697, USA.
出版信息
J Virol. 1998 Oct;72(10):8420-4. doi: 10.1128/JVI.72.10.8420-8424.1998.
Abstract
L-Chicoric acid is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase in vitro and of HIV-1 replication in tissue culture. Following 3 months of selection in the presence of increasing concentrations of L-chicoric acid, HIV-1 was completely resistant to the compound. Introduction of the mutant integrase containing a single glycine-to-serine amino acid change at position 140 into the native, L-chicoric acid-sensitive virus demonstrated that this change was sufficient to confer resistance to L-chicoric acid. These results confirm through natural selection previous biochemical studies showing that L-chicoric acid inhibits integrase and that the drug is likely to interact at residues near the catalytic triad in the integrase active site.
摘要
L-菊苣酸在体外是1型人类免疫缺陷病毒（HIV-1）整合酶的抑制剂，在组织培养中可抑制HIV-1复制。在浓度不断增加的L-菊苣酸存在下进行3个月的筛选后，HIV-1对该化合物完全耐药。将在第140位含有单个甘氨酸到丝氨酸氨基酸变化的突变整合酶引入天然的、对L-菊苣酸敏感的病毒中，结果表明这种变化足以赋予对L-菊苣酸的耐药性。这些结果通过自然选择证实了先前的生化研究，即L-菊苣酸抑制整合酶，并且该药物可能在整合酶活性位点催化三联体附近的残基处相互作用。
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