Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance
Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance
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DOI：
10.1086/515282
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发表时间：
1998-05-01
影响因子：
6.4
通讯作者：
Mitsuya, H
中科院分区：
文献类型：
--
作者：
Maeda, Y;Venzon, DJ;Mitsuya, H
进行研究以确定当病毒在pol基因中获得赋予对多种双脱氧核苷的抗性的一组或五个突变子集（A62 V、V75 I、F77 L、F116 Y和Q151 M）时，人类免疫缺陷病毒（HIV）-1的复制动力学是否改变。在没有药物的情况下，产生的所有感染性克隆的复制率与野生型HIV-1的复制率相当。然而，在存在齐多夫定或去羟肌苷的情况下，复制的比较顺序是HIV-1（62/75/77/116/151）> HIV-1（77/116/151）> HIV-1（75/77/116/151）与HIV-1（151）近似，而耐药性为HIV-1（75/77/116/151）> HIV-1（62/75/77/116/151）大于或等于HIV-1（77/116/151）> HIV-1（151）。这些感染性突变体的病毒学特征表明，HIV-1通过一个或多个突变产生耐药性，然而，这牺牲了复制能力;然后，当多双脱氧核苷抗性突变体出现时，它最终通过额外的突变获得最佳复制能力。
Investigations were done to determine whether the replication kinetics of human immunodeficiency virus (HIV)-1 were altered when the virus acquired a set or subsets of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene conferring resistance to multiple dideoxynucleosides. In the absence of drugs, the replication rate of all infectious clones generated was comparable to that of wild type HIV-1. However, in the presence of zidovudine or didanosine, the comparative order for replication was HIV-1(62/75/77/116/151) > HIV-1(77/116/151) > HIV-1(75/77/116/151) approximate to HIV-1(151), whereas that for drug resistance was HIV-1(75/77/116/151) > HIV-1(62/75/77/116/151) greater than or equal to HIV-1(77/116/151) > HIV-1(151). The virologic features of these infectious mutants suggest that HIV-1 develops drug resistance through one or more mutations, which, however, sacrifice replicative capability; then it finally acquires optimal replication competence by additional mutations when the multi-dideoxynucleoside-resistant mutant emerges.