编码对2',3'-双脱氧肌苷和2',3'-双脱氧胞苷低水平1型人类免疫缺陷病毒耐药性的相同突变，赋予对2',3'-双脱氧-3'-硫代胞苷(-)对映体的高水平耐药性。
The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.
作者信息
Gao Q, Gu Z, Parniak M A, Cameron J, Cammack N, Boucher C, Wainberg M A
机构信息
Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada.
出版信息
Antimicrob Agents Chemother. 1993 Jun;37(6):1390-2. doi: 10.1128/AAC.37.6.1390.
Abstract
Variants of human immunodeficiency virus type 1 that display 500- to 1,000-fold resistance to the (-) enantiomer of 2'-deoxy-3'-thiacytidine and approximately 4- to 8-fold resistance to 2',3'-dideoxycytidine and 2',3'-dideoxyinosine have been generated through in vitro selection with the former compound. The polymerase regions of several of these resistant viruses shared a codon alteration at site 184 (ATG-->GTG; methionine-->valine), a mutation previously associated with low-level resistance to 2',3'-dideoxycytidine. The biological relevance of this mutation for the (-) enantiomer of 2'-deoxy-3'-thiacytidine was confirmed by site-directed mutagenesis with the HXB2-D clone of human immunodeficiency virus type 1.
摘要
通过用2'-脱氧-3'-硫代胞苷的（-）对映体进行体外筛选，已产生了对2'-脱氧-3'-硫代胞苷的（-）对映体表现出500至1000倍抗性、对2'，3'-二脱氧胞苷和2'，3'-二脱氧肌苷表现出约4至8倍抗性的1型人类免疫缺陷病毒变体。其中几种抗性病毒的聚合酶区域在184位点共享一个密码子改变（ATG→GTG；甲硫氨酸→缬氨酸），这是一个先前与对2'，3'-二脱氧胞苷低水平抗性相关的突变。用1型人类免疫缺陷病毒的HXB2-D克隆进行定点诱变，证实了该突变对2'-脱氧-3'-硫代胞苷（-）对映体的生物学相关性。
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