Potter Simon J, Lemey Philippe, Dyer Wayne B, Sullivan John S, Chew Choo Beng, Vandamme Anne-Mieke, Dwyer Dominic E, Saksena Nitin K
Retroviral Genetics Laboratory, Center for Virus Research, Westmead Millennium Institute, Westmead Hospital, The University of Sydney, Darcy Road, Westmead, Sydney NSW 2145, Australia.
Virology. 2006 Apr 25;348(1):35-46. doi: 10.1016/j.virol.2005.12.031. Epub 2006 Feb 7.
HIV-1 infection and compartmentalization in diverse leukocyte targets significantly contribute to viral persistence during suppressive highly active antiretroviral therapy (HAART). Longitudinal analyses were performed on envelope sequences of HIV-1 populations from plasma, CD4+ and CD8+ T lymphocytes in 14 patients receiving HAART and 1 therapy-naive individual. Phylogenetic reconstructions and analysis of molecular variance revealed that HIV-1 populations in CD4+ and CD8+ T cells remained compartmentalized over time in most individuals. Analyses of viral genetic variation demonstrated that, despite compartmentalization remaining over time, viral subpopulations tended not to persist and evolve but instead broke down and became reconstituted by new founder viruses. Due to the profound impact of HAART on viral evolution, it was difficult to discern whether these dynamics were ongoing during treatment or predominantly established prior to the commencement of therapy. The genetic structure and viral founder effects observed in serially sampled T lymphocyte populations supported a scenario of metapopulation dynamics in the tissue(s) where different leukocytes become infected, a factor likely to contribute to the highly variable way that drug resistance evolves in different individuals during HAART.
在接受高效抗逆转录病毒疗法（HAART）抑制治疗期间，HIV-1在多种白细胞靶标中的感染和分隔显著促进了病毒的持续存在。对14例接受HAART治疗的患者以及1例未经治疗的个体的血浆、CD4+和CD8+ T淋巴细胞中HIV-1群体的包膜序列进行了纵向分析。系统发育重建和分子方差分析显示，在大多数个体中，CD4+和CD8+ T细胞中的HIV-1群体随时间推移仍保持分隔状态。病毒遗传变异分析表明，尽管随时间推移分隔状态依然存在，但病毒亚群往往不会持续存在和进化，而是分解并由新的奠基病毒重新构成。由于HAART对病毒进化有深远影响，很难辨别这些动态变化是在治疗期间持续存在，还是主要在治疗开始前就已确立。在连续采样的T淋巴细胞群体中观察到的遗传结构和病毒奠基效应支持了一种在不同白细胞被感染的组织中存在集合种群动态变化的情况，这一因素可能导致在HAART期间不同个体中耐药性以高度可变的方式演变。
