Early Emergence and Long-Term Persistence of HIV-Infected T-Cell Clones in Children.
Early Emergence and Long-Term Persistence of HIV-Infected T-Cell Clones in Children.
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DOI：
10.1128/mbio.00568-21
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发表时间：
2021-04-08
期刊：
影响因子：
6.4
通讯作者：
Kearney MF
中科院分区：
文献类型：
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作者：
Bale MJ;Katusiime MG;Wells D;Wu X;Spindler J;Halvas EK;Cyktor JC;Wiegand A;Shao W;Cotton MF;Hughes SH;Mellors JW;Coffin JM;Van Zyl GU;Kearney MF
HIV-1将其基因组整合到宿主细胞的DNA中。因此，HIV-1基因组在细胞分裂期间与宿主细胞DNA一起复制。对围产期感染儿童中人类免疫缺陷病毒（HIV）感染T细胞克隆的出现和持续性知之甚少。我们分析了11名年龄在1.8至17.4个月之间开始抗逆转录病毒治疗（ART）并抑制病毒血症6至9年的儿童的外周血单核细胞（PBMC）克隆扩增。我们从ART前样本中获得了8，662个HIV-1整合位点，从ART样本中获得了1，861个位点。在10/11名儿童中，在ART前检测到感染细胞的扩增克隆。在8名儿童中，ART前检测到的感染细胞克隆在ART上持续了6至9年。ART上获得的样品中的整合位点与离体感染的健康供体PBMC的比较显示了对BACH 2和STAT 5 B中整合有前病毒的细胞的选择。我们的分析表明，尽管儿童和成人之间的T细胞组成和动力学存在显着差异，但HIV感染的细胞克隆在儿童早期建立，在ART上持续长达9年，并且可以由原癌基因中的前病毒整合驱动。
HIV-1 integrates its genome into the DNA of host cells. Consequently, HIV-1 genomes are copied with the host cell DNA during cellular division. Little is known about the emergence and persistence of human immunodeficiency virus (HIV)-infected T-cell clones in perinatally infected children. We analyzed peripheral blood mononuclear cells (PBMCs) for clonal expansion in 11 children who initiated antiretroviral therapy (ART) between 1.8 and 17.4 months of age and with viremia suppressed for 6 to 9 years. We obtained 8,662 HIV type 1 (HIV-1) integration sites from pre-ART samples and 1,861 sites from on-ART samples. Expanded clones of infected cells were detected pre-ART in 10/11 children. In 8 children, infected cell clones detected pre-ART persisted for 6 to 9 years on ART. A comparison of integration sites in the samples obtained on ART with healthy donor PBMCs infected ex vivo showed selection for cells with proviruses integrated in BACH2 and STAT5B. Our analyses indicate that, despite marked differences in T-cell composition and dynamics between children and adults, HIV-infected cell clones are established early in children, persist for up to 9 years on ART, and can be driven by proviral integration in proto-oncogenes.