Rates and dates of divergence between AIDS virus nucleotide sequences.

Rates and dates of divergence between AIDS virus nucleotide sequences.
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DOI:
10.1093/oxfordjournals.molbev.a040503
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发表时间:
1988-07
影响因子:
10.7
通讯作者:
Wenhao Li;M. Tanimura;P. Sharp
Wenhao Li;M. Tanimura;P. Sharp
中科院分区:
生物学1区
文献类型:
--
作者:
Wenhao Li;M. Tanimura;P. Sharp

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由一种称为人类免疫缺陷病毒(HIV)的逆转录病毒引起的获得性免疫缺陷综合征(AIDS)已成为一种流行病。了解艾滋病毒中核苷酸替换的速率以及病毒传播的历史和模式对于了解艾滋病的流行病学和发病机理以及开发治疗和疫苗战略都是重要的。已经开发了一种新的模型,用于估计艾滋病毒基因组不同区域的替代率。编码衣壳蛋白和逆转录酶的区域的非同义(氨基酸改变)取代率最低,约为1.7 × 10(-3)个核苷酸取代/位点/年。在包膜基因的高变区,非同义率极高(14 × 10 ~(-3)),表明病毒抗原性变化极快。其它编码区的非同义率在3 × 10 ~(-3)~ 7 × 10 ~(-3)之间。HIV基因组的平均同义率为10 × 10(-3)。这些比率比DNA基因组中的比率高10(6)倍,并且至少与其他RNA病毒中的比率一样高。证据提供了一个不同的艾滋病毒株之间的重组的情况下。我们的分析表明,艾滋病病毒在1960年之前就存在于中非,并在20世纪70年代中期之前传播到北美。从核苷酸序列数据推断出HIV分离株之间的进化关系,结果与艾滋病从海地传播到美国的观点一致。
The acquired immune deficiency syndrome (AIDS), caused by a retrovirus called human immunodeficiency virus (HIV), has become a pandemic. A knowledge of the rate of nucleotide substitution in HIV and of the history and pattern of spread of the virus is important for understanding the epidemiology and pathogenesis of AIDS and for developing therapies and vaccine strategies. A new model has been developed and used to estimate the substitution rates in various regions in the HIV genome. The rate of nonsynonymous (amino acid-changing) substitution is lowest in the regions coding for the capsid proteins and the reverse transcriptase, being approximately 1.7 X 10(-3) nucleotide substitutions/site/year. The nonsynonymous rate is extremely high (14 X 10(-3] in the hypervariable regions of the envelope gene, suggesting extremely rapid change in viral antigenicity. The nonsynonymous rates in the other coding regions are between 3 X 10(-3) and 7 X 10(-3). The average synonymous rate for the HIV genome is 10 X 10(-3). These rates are 10(6) times greater than the rates in DNA genomes and at least as high as the rates in other RNA viruses. Evidence is provided for a case of recombination between different HIV strains. Our analysis suggests that the AIDS virus had existed in central Africa before 1960 and spread to North America before the mid 1970s. The evolutionary relationships among HIV isolates are inferred from nucleotide sequence data, and the result is consistent with the view that AIDS spread from Haiti to the United States.