Saag M S, Hahn B H, Gibbons J, Li Y, Parks E S, Parks W P, Shaw G M
Department of Internal Medicine, University of Alabama, Birmingham 35294.
Nature. 1988 Aug 4;334(6181):440-4. doi: 10.1038/334440a0.
Genotypic variation among independent isolates of human immunodeficiency virus type-1 (HIV-1) is well known, but its molecular basis and biological consequences are poorly understood. We examined the genesis of molecular variation in HIV-1 by sequential virus isolations from two chronically infected individuals and analysis of recombinant HIV-1 genomic clones. In three different virus isolates full-length HIV-1 clones were identified and found to consist, respectively, of 17, 9 and 13 distinguishable, but highly-related, viral genotypes. Thirty-five viral clones derived from two HIV-1 isolates obtained from the same individual but 16 months apart showed progressive change, yet were clearly related. Similar changes in the HIV-1 genome did not occur in vitro during virus isolation and amplification. The results indicate that HIV-1 variation in vivo is rapid, that a remarkably large number of related but distinguishable genotypic variants evolve in parallel and coexist during chronic infection, and that 'isolates' of HIV-1, unless molecularly or biologically cloned, generally consist of complex mixtures of genotypically distinguishable viruses.
人类免疫缺陷病毒1型（HIV-1）独立分离株之间的基因型变异是众所周知的，但其分子基础和生物学后果却知之甚少。我们通过从两名慢性感染个体中连续进行病毒分离以及对重组HIV-1基因组克隆进行分析，研究了HIV-1分子变异的起源。在三种不同的病毒分离株中，鉴定出了全长HIV-1克隆，发现它们分别由17种、9种和13种可区分但高度相关的病毒基因型组成。从同一患者身上相隔16个月获得的两种HIV-1分离株衍生出的35个病毒克隆显示出渐进性变化，但明显相关。在病毒分离和扩增过程中，HIV-1基因组在体外未发生类似变化。结果表明，HIV-1在体内的变异迅速，在慢性感染期间，大量相关但可区分的基因型变异体平行进化并共存，并且除非进行分子或生物学克隆，HIV-1的“分离株”通常由基因型可区分的病毒的复杂混合物组成。
