Slower evolution of human immunodeficiency virus type I quasispecies during progression to AIDS
Slower evolution of human immunodeficiency virus type I quasispecies during progression to AIDS
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DOI：
10.1128/jvi.71.10.7498-7508.1997
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发表时间：
1997-10-01
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;Pan, H;Mullins, JI
采用DNA异双工迁移率测定方法，研究了CD4（+）细胞计数下降率不同的2例男性和感染日期不详的6例男性从感染时间开始，包膜基因准种的进化。准种在接近血清转化时具有遗传同质性。随后，较慢的前病毒遗传多样化和较高的血浆病毒血症与CD4（+）细胞计数的快速下降相关。除了进展最快的艾滋病患者外，所有受试者在3至4年内都出现了高度多样化的准种。高准种多样性随后维持数年，直到在晚期艾滋病患者中再次变得更加均匀。保持高CD4（+）细胞计数的个体显示其复杂的前病毒准种的持续遗传转换，而在严重免疫功能低下患者的纵向样本中发现了更密切相关的变异集。在短长度的PBMC共培养中生长出的有限数量的变异在未培养的健康的原病毒准种中是罕见的。长期感染个体，但更常见于体内CD4（+）细胞计数低的患者。在快速发展为艾滋病和晚期患者中观察到的HIV-1进化较慢可能反映了宿主介导的复制准物种的无效选择压力。
The evolution of human immunodeficiency virus type 1 (HIV-1) quasispecies at the envelope gene was studied from the time of infection in II men who experienced different rates of CD4(+) cell count decline and 6 men with unknown dates of infection by using DNA heteroduplex mobility assays. Quasispecies were genetically homogeneous near the time of seroconversion. Subsequently slower proviral genetic diversification and higher plasma viremia correlated with rapid CD4(+) cell count decline, Except for the fastest progressors to AIDS, highly diverse quasispecies del eloped in all subjects within 3 to 4 years. High quasispecies diversity was then maintained for years until again becoming more homogeneous in a subset of late-stage AIDS patients, Individuals who maintained high CD4(+) cell counts showed continuous genetic turnover of their complex proviral quasispecies, while more closely related sets of variants were found in longitudinal samples of severely immunocompromised patients, The limited number of variants that grew out in short-tel nl PBMC cocultures were rare in the uncultured proviral quasispecies of healthy. long-term infected individuals but more common in vivo in patients with low CD4(+) cell counts. The slower evolution of HIV-1 observed during rapid progression to AIDS and in advanced patients may reflect ineffective host-mediated selection pressures on replicating quasispecies.