Mitochondrial DNA mutations accumulated in HIV-1-infected children who have an excellent virological response when exposed to long-term antiretroviral therapy.
Mitochondrial DNA mutations accumulated in HIV-1-infected children who have an excellent virological response when exposed to long-term antiretroviral therapy.
复制标题
HIV-1感染儿童中线粒体DNA突变积累，这些儿童在接受长期抗逆转录病毒治疗时具有良好的病毒学反应。
DOI：
10.1093/jac/dky282
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发表时间：
2018
影响因子：
5.2
通讯作者：
Chen Dexi
中科院分区：
文献类型：
--
作者：
Ouyang Yabo;Wei Feili;Qiao Luxin;Liu Kai;Dong Yaowu;Guo Xianghua;Wang Shanshan;Pang Lijun;Lin Minghua;Zhang Fujie;Lin Dongdong;Chen Dexi
目的HIV-1感染儿童长期接触NRTI后线粒体DNA （mtDNA）发生突变的可能性越来越受到关注。方法回顾性分析24例开始抗逆转录病毒治疗2年以上且病毒学应答良好且未改变治疗方案的HIV-1感染儿童。包括2009年（T1）、2010年（T2）和2013年（T3）相应的pbmc。利用新一代测序技术对整个mtDNA进行测序，揭示了mtDNA变异谱。结果ART期间mtDNA突变数T1 < T2 < T3 (P =0.086)；有趣的是，T3的全mtDNA突变数（中位数41，范围24-62）显著高于T1 （34, 25-46,P =0.029）。mtDNA总突变数与治疗时间呈正相关（r=0.352,P =0.002）。在观察期间，mtDNA突变更多地发生在d环、细胞色素b （CYTB）和12S rRNA区域。CYTB和12S rRNA中T3的异质比高于T1 （P=0.034和P=0.042）。在nt 263 （A263G, D-loop）和nt 8860 （A8860G, ATPase6）上发现了较高的异质群体水平。T1、T2和T3的异质性在nt 14783发生显著差异（T14783C， CYTB，P=0.048, T3 > T2 > T1）。结论我们的研究结果揭示了hiv -1感染儿童的mtDNA变异谱，这些儿童具有良好的病毒学应答。抗逆转录病毒治疗过程中积累的mtDNA突变可能在促进线粒体功能障碍的发生中起重要作用。
ObjectivesThere is growing concern about mitochondrial DNA (mtDNA) mutations with long-term NRTI exposure in HIV-1 infected children.MethodsTwenty-four HIV-1 infected children who started ART more than 2 years earlier who had an excellent virological response and had not changed their regimen were enrolled retrospectively. Their corresponding PBMCs in 2009 (T1), 2010 (T2) and 2013 (T3) were included. Sequencing of the entire mtDNA using next-generation sequencing revealed the spectrum of mtDNA variants.ResultsThe trend showed that the number of mtDNA mutations during ART occurred as T1 < T2 < T3 (P =0.086). Interestingly, the numbers of whole mtDNA mutations at T3 (median 41, range 24–62) were significantly greater than at T1 (34, 25–46,P =0.029). A positive correlation was found between total mtDNA mutations and treatment time (r=0.352,P =0.002). During the observation period, mtDNA mutations more frequently occurred in the D-loop, cytochrome b (CYTB) and 12S rRNA regions. The heteroplasmic ratio of T3 was higher than that of T1 in CYTB and 12S rRNA (P=0.034 andP=0.042, respectively). High heteroplasmic population levels were found at nt 263 (A263G, D-loop) and nt 8860 (A8860G, ATPase6). A significant difference in heteroplasmy between T1, T2 and T3 occurred at nt 14783 (T14783C, CYTB,P=0.048, T3 > T2 > T1).ConclusionsOur findings reveal the spectrum of mtDNA variants in HIV-1-infected children who had an excellent virological response. mtDNA mutations accumulated during ART may play an important role in facilitating the occurrence of mitochondrial dysfunction.