Independent evolution of the env and pol genes of HIV‐1 during zidovudine therapy
Independent evolution of the env and pol genes of HIV‐1 during zidovudine therapy
复制标题
齐多夫定治疗期间 HIV-1 的 env 和 pol 基因的独立进化
DOI：
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
A. Cleland
中科院分区：
文献类型：
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作者：
A. Leigh Brown;A. Cleland
目的：确定HIV-1 pol基因抗病毒耐药选择对env V3区变异水平和进化模式的影响。设计图：前病毒基因组从两个病人之前，期间和之后终止齐多夫定（ZDV）治疗（约2年）进行了扩增和测序的pol和env，和进化的V3高变区相比，逆转录酶结构域的pol。方法：基因片段进行聚合酶链反应扩增患者的外周血单核细胞。使用T7 DNA聚合酶和染料标记的终止子在自动DNA测序仪上进行核苷酸测序。序列进行了分析，使用最大似然系统发育技术。结果：两名患者在ZDV治疗1年后均显示出多种耐药相关突变。V3序列多样性在处理期间未显示降低。在该区域继续发生实质性变化，并且在两名患者中均存在多个谱系，与在一名患者（患者74）的pol基因中观察到的单一谱系相反，通过似然比检验证实了差异。结论：本研究没有证据表明抗病毒药物的选择对env基因的进化有任何显着影响。这些基因的独立进化意味着在研究期间这两个基因之间发生了重组。在开发涉及多个靶基因的HIV治疗策略时，应该考虑到这种独立的进化。
Objective: To determine the effect that selection for antiviral resistance in the HIV‐1 pol gene has on the level of variation and pattern of evolution in the V3 region of env. Design: Proviral genomes obtained from two patients before, during and after the termination of zidovudine (ZDV) therapy (approximately 2 years) were amplified and sequenced in pol and env, and the evolution of the V3 hypervariable region compared with that of the reverse transcriptase domain of pol. Methods: Gene fragments were polymerase chain reaction‐amplified from patients' peripheral blood mononuclear cells. Nucleotide sequencing was carried out using T7 DNA polymerase and dye‐labelled terminators on an automated DNA sequencer. Sequences were analysed using maximum likelihood phylogenetic techniques. Results: Both patients showed multiple resistance‐associated mutations after 1 year of ZDV therapy. Sequence diversity in V3 showed no reduction during the period of treatment. Substantial change continued to occur in this region and multiple lineages were present in both patients, in contrast to the single lineage observed in the pol gene of one (patient 74), a difference confirmed by likelihood ratio tests. Conclusions: There is no evidence from this study that selection due to antivirals has any significant impact on the evolution of the env gene. The independence in the evolution of these genes implies that recombination was occurring between the two genes during the study period. Such independent evolution should be allowed for in developing strategies for HIV therapy involving multiple target genes.