HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EVOLUTION IN-VIVO TRACKED BY DNA HETERODUPLEX MOBILITY ASSAYS
HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EVOLUTION IN-VIVO TRACKED BY DNA HETERODUPLEX MOBILITY ASSAYS
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DOI：
10.1128/jvi.68.10.6672-6683.1994
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发表时间：
1994-10-01
影响因子：
5.4
通讯作者：
MULLINS, JI
中科院分区：
文献类型：
--
作者：
DELWART, EL;SHEPPARD, HW;MULLINS, JI
体内对人类免疫缺陷病毒施加的高突变率和强大的选择压力导致了被称为准种的遗传变异库的形成。DNA异源双链迁移率和跟踪分析用于监测HIV序列多样性的产生，估计准物种的复杂性，并评估遗传变异的周转，以接近了解体内病毒准物种进化和疾病进展之间的关系。性传播后不久，前病毒DNA池几乎是同质的。然后，个体变异的出现和清除在不同的个体中以不同的速度发生。在长期感染、无症状的个体中发现了较高的准种复杂性，而快速的CD4(+)细胞下降和艾滋病通常但不总是相关，其准种复杂性较低。在体外培养后，前病毒的遗传变异通常很低，这是因为一个或几个变异体的产生，这些变体往往只是在后来作为前病毒在外周血单核细胞中变得更加丰富。这些研究提供了对体内人类免疫缺陷病毒序列变化的动态的洞察，并说明了异源双链分析在研究与快速遗传变化相关的现象方面的应用。
High mutation rates and strong selective pressures imposed on human immunodeficiency viruses in vivo result in the formation of pools of genetic variants known as quasispecies. DNA heteroduplex mobility and tracking analyses were used to monitor the generation of HIV sequence diversity, to estimate quasispecies complexity, and to assess the turnover of genetic variants to approach an understanding of the relationship between viral quasispecies evolution in vivo and disease progression. Proviral DNA pools were nearly homogeneous soon after sexual transmission. The emergence and clearance of individual variants then occurred at different rates in different individuals. High quasispecies complexity was found in long-term-infected, asymptomatic individuals, while rapid CD4(+) cell decline and AIDS were often, but not always, associated,vith lower quasispecies complexity. Proviral genetic variation was often low following in vitro culture, because of the outgrowth of one or a few variants that often became more abundant only later as proviruses in peripheral blood mononuclear cells. These studies provide insight into the dynamics of human immunodeficiency virus sequence changes in vivo and illustrate the utility of heteroduplex analysis for the study of phenomena associated with rapid genetic changes.