High frequency of mitochondrial DNA mutations in HIV-infected treatment-experienced individuals.
High frequency of mitochondrial DNA mutations in HIV-infected treatment-experienced individuals.
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DOI：
10.1111/hiv.12390
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发表时间：
2017-01
期刊：
影响因子：
3
通讯作者：
Paintsil E
中科院分区：
文献类型：
--
作者：
Li M;Foli Y;Liu Z;Wang G;Hu Y;Lu Q;Selvaraj S;Lam W;Paintsil E
我们最近观察到在接受抗逆转录病毒治疗（ART）的HIV感染者中脱氧核糖核苷酸（dNTP）池的减少。在细胞培养和动物模型中，dNTPs的改变导致线粒体DNA （mtDNA）的突变。因此，我们研究了ART是否与HIV感染治疗经历个体外周血单核细胞（PBMCs）线粒体基因组序列变异相关。在这个病例对照研究的亚研究中，纳入了71名参与者：22例“病例”，他们是有线粒体毒性的HIV感染治疗经历的患者，25例没有线粒体毒性的HIV感染治疗经历的患者，以及24例未感染HIV的对照组。从pbmc中提取总DNA，纯化的聚合酶链反应（PCR）产物使用PacBio单分子实时（SMRT）测序技术进行第三代测序。这些序列与修订后的剑桥人线粒体DNA参考序列（NC_012920.1）比对，用于检测变异。我们共鉴定出123个新的变异，其中39个在编码区。与未感染艾滋病毒的对照组相比，接受过艾滋病毒感染治疗的有毒性和无毒性患者的线粒体变异平均数量显著高于未感染艾滋病毒的对照组。我们观察到，与未感染HIV的对照组相比，接受过HIV感染治疗的毒性患者的mtDNA大规模缺失负担更高（P = 0.02）。与未感染HIV的对照组相比，感染HIV治疗的毒性患者中含有共同缺失（mt.δ4977）的mtDNA分子的频率更高（P = 0.06）。在有和没有毒性的HIV感染治疗经历的患者中，mtDNA变异没有统计学上的显著差异。mtDNA变异（突变和大规模缺失）的频率在有或没有ART诱导毒性的HIV感染治疗经历的患者中高于未感染的对照组。
We recently observed a decrease in deoxyribonucleotide (dNTP) pools in HIV‐infected individuals on antiretroviral therapy (ART). Alterations in dNTPs result in mutations in mitochondrial DNA (mtDNA) in cell culture and animal models. Therefore, we investigated whether ART is associated with mitochondrial genome sequence variation in peripheral blood mononuclear cells (PBMCs) of HIV‐infected treatment‐experienced individuals. In this substudy of a case−control study, 71 participants were included: 22 ‘cases’, who were HIV‐infected treatment‐experienced patients with mitochondrial toxicity, 25 HIV‐infected treatment‐experienced patients without mitochondrial toxicity, and 24 HIV‐uninfected controls. Total DNA was extracted from PBMCs and purified polymerase chain reaction (PCR) products were subjected to third‐generation sequencing using the PacBio Single Molecule Real‐Time (SMRT) sequencing technology. The sequences were aligned against the revised Cambridge reference sequence for human mitochondrial DNA (NC_012920.1) for detection of variants. We identified a total of 123 novel variants, 39 of them in the coding region. HIV‐infected treatment‐experienced patients with and without toxicity had significantly higher average numbers of mitochondrial variants per participant than HIV‐uninfected controls. We observed a higher burden of mtDNA large‐scale deletions in HIV‐infected treatment‐experienced patients with toxicity compared with HIV‐uninfected controls (P = 0.02). The frequency of mtDNA molecules containing a common deletion (mt.δ4977) was higher in HIV‐infected treatment‐experienced patients with toxicity compared with HIV‐uninfected controls (P = 0.06). There was no statistically significant difference in mtDNA variants between HIV‐infected treatment‐experienced patients with and without toxicity. The frequency of mtDNA variants (mutations and large‐scale deletions) was higher in HIV‐infected treatment‐experienced patients with or without ART‐induced toxicity than in uninfected controls.
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影响因子：
158.5
作者：
MORAES, CT;DIMAURO, S;ROWLAND, LP
通讯作者：
ROWLAND, LP
影响因子：
11.2
作者：
Naviaux, RK;Nguyen, KV
通讯作者：
Nguyen, KV
DOI：
10.1097/qai.0b013e3181a324d6
发表时间：
2009-06-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Hendrickson SL;Kingsley LA;Ruiz-Pesini E;Poole JC;Jacobson LP;Palella FJ;Bream JH;Wallace DC;O'Brien SJ
通讯作者：
O'Brien SJ
影响因子：
3.8
作者：
McComsey, G;Tan, DJ;Wong, LJ
通讯作者：
Wong, LJ
影响因子：
168.9
作者：
Fellay, J;Boubaker, K;Telenti, A
通讯作者：
Telenti, A