GENETIC-VARIATION IN HTLV-III/LAV OVER TIME IN PATIENTS WITH AIDS OR AT RISK FOR AIDS
GENETIC-VARIATION IN HTLV-III/LAV OVER TIME IN PATIENTS WITH AIDS OR AT RISK FOR AIDS
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DOI：
10.1126/science.3012778
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发表时间：
1986-06-20
期刊：
影响因子：
56.9
通讯作者：
PARKS, WP
中科院分区：
文献类型：
--
作者：
HAHN, BH;SHAW, GM;PARKS, WP
在一项研究中，遗传变异的艾滋病病毒，HTLV-III/LAV，连续病毒分离株从持续感染的个人进行了检查，Southern印迹基因组分析，分子克隆和核苷酸测序。在1年或2年的时间内，从3名个体中的每一个获得4至6个病毒分离株。在整个病毒基因组中检测到变化，包括孤立和成簇的核苷酸点突变以及短缺失或插入。基因组限制性酶切图谱和核苷酸序列比较的结果表明，顺序分离的病毒是从共同的祖先病毒平行进化而来的。据估计，HTLV-III/LAV的进化速率为env基因每年每个位点至少10-3个核苷酸替换，gag基因为10-4个，比大多数DNA基因组的值大100万倍。尽管序列差异的速度相对较快，但来自任何一个患者的病毒分离物彼此之间的相关性都比来自其他个体的病毒要大得多。鉴于大多数独立的HTLV-III/LAV分离株之间的实质性异质性，从给定个体中仅重复分离高度相关的病毒提高了某种类型的干扰机制可能防止病毒的一种以上主要基因型形式同时感染的可能性。
In a study of genetic variation in the AIDS virus, HTLV-III/LAV, sequential virus isolates from persistently infected individuals were examined by Southern blot genomic analysis, molecular cloning, and nucleotide sequencing. Four to six virus isolates were obtained from each of three individuals over a 1-year or 2-year period. Changes were detected throughout the viral genomes and consisted of isolated and clustered nucleotide point mutations as well as short deletions or insertions. Results from genomic restriction mapping and nucleotide sequence comparisons indicated that viruses isolated sequentially had evolved in parallel from a common progenitor virus. The rate of evolution of HTLV-III/LAV was estimated to be at least 10-3 nucleotide substitutions per site per year for the env gene and 10-4 for the gag gene, values a millionfold greater than for most DNA genomes. Despite this relatively rapid rate of sequence divergence, virus islates from any one patient were all much more related to each other than to viruses from other individuals. In view of the substantial heterogeneity among most independent HTLV-III/LAV isolates, the repeated isolation from a given individual of only highly related viruses raises the possibility that some type of interference mechanism may prevent simultaneous infection by more than one major genotypic form of the virus.