Human immunodeficiency virus type 1 genetic evolution in children with different rates of development of disease
Human immunodeficiency virus type 1 genetic evolution in children with different rates of development of disease
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DOI：
10.1128/jvi.71.1.663-677.1997
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发表时间：
1997-01-01
影响因子：
5.4
通讯作者：
Wolinsky, SM
中科院分区：
文献类型：
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作者：
Ganeshan, S;Dickover, RE;Wolinsky, SM
在感染人类免疫缺陷病毒I型(HIV-1)的儿童中，疾病的发展速度差别很大。这些观察到的差异的原因尚不清楚，但最可能取决于HIV-1准物种病毒种群和宿主施加的免疫限制之间的动态相互作用。为了研究疾病进展与遗传多样性之间的关系，我们分析了6名围产期感染儿童的病毒序列进化，方法是通过对连续访问获得的血液样本进行聚合酶链式反应(PCR)检测跨越病毒包膜基因C2至V5区的前病毒序列。克隆每个儿童4个样本时间点的聚合酶链式反应产物DNA，对每个样本10~13个克隆进行测序。与病毒粒子相关RNA负荷高且进展迅速的儿童相比，病毒粒子相关RNA负荷低且进展缓慢的儿童与感染时间相比存在更大的遗传距离。在系统发育重建中观察到的较大的分支长度与每个潜在的非同义位点上的非同义碱基替换的累积速率有关，这与对改变的正选择一致，而不是复制动力学上的差异。疾病进展缓慢的儿童的病毒序列也显示出与不同采样时间相关的聚集的趋势。病毒种群的这些渐进性变化在快速发展为疾病的儿童的病毒序列中没有发现。因此，尽管HIV-1准种是一个多样化、快速进化和相互竞争的遗传变异群体，但在不同的选择限制下，可以发现不同的遗传进化速度。这些数据表明，HIV-1准物种病毒种群所表现出的进化动态与自然选择约束下进化的达尔文系统是相容的。
The rate of development of disease varies considerably among human immunodeficiency virus type I (HIV-1)-infected children. The reasons for these observed differences are not clearly understood but most probably depend on the dynamic interplay between the HIV-1 quasispecies virus population and the immune constraints imposed by the host. To study the relationship between disease progression and genetic diversity, we analyzed the evolution of viral sequences within six perinatally infected children by examining proviral sequences spanning the C2 through V5 regions of the viral envelope gene by PCR of blood samples obtained at sequential visits. PCR product DNAs from four sample time points per child were cloned, and 10 to 13 clones from each sample were sequenced. Greater genetic distances relative to the time of infection were found for children with low virion-associated RNA burdens and slow progression to disease relative to those found for children with high virion-associated RNA burdens and rapid progression to disease. The greater branch lengths observed in the phylogenetic reconstructions correlated with a higher accumulation rate of nonsynonymous base substitutions per potential nonsynonymous site, consistent with positive selection for change rather than a difference in replication kinetics. Viral sequences from children with slow progression to disease also showed a tendency to form clusters that associated with different sampling times. These progressive shifts in the viral population were not found in viral sequences from children with rapid progression to disease. Therefore, despite the HIV-1 quasispecies being a diverse, rapidly evolving, and competing population of genetic variants, different rates of genetic evolution could be found under different selective constraints. These data suggest that the evolutionary dynamics exhibited by the HIV-1 quasispecies virus populations are compatible with a Darwinian system evolving under the constraints of natural selection.