Mitochondrial DNA mutations in blood samples from HIV-1-infected children undergoing long-term antiretroviral therapy

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• 作者：Yabo Ouyang^a ; ^b ; ¹ ; Luxin Qiao^a ; ^b ; ¹ ; Kai Liu^a ; ^b ; Yunjin Zang^a ; Yu Sun^a ; Yaowu Dong^d ; Daojie Liu^a ; ^b ; Xianghua Guo^a ; ^b ; Feili Wei^a ; ^b ; Minghua Lin^a ; ^b ; Fujie Zhang^c ; ; Dexi Chen^a ; ^b ; ^{dexichen@ccmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HIV-1-infected children ; Antiretroviral therapy ; Mitochondrial DNA ; Mutation
• 刊名：Mutation Research/Genetic Toxicology and Environmental Mutagenesis
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：805
• 期：Complete
• 页码：1-6
• 全文大小：917 K

文摘

We have analyzed mutations in whole mitochondrial (mt) genomes of blood samples from HIV-1-infected children treated with long-term antiretroviral therapy (ART), who had an excellent virological response. HIV-1-infected children who have undergone ART for 4 y with an excellent virological response (group A; 15 children) and ten healthy children (controls) without HIV-1 infection were enrolled retrospectively. Peripheral blood mononuclear cells (PBMCs) were obtained and mt DNA mutations were studied. The total number of mtDNA mutations in group A was 3 H more than in the controls (59 vs. 19, P < 0.001) and the same trend was seen in all mtDNA regions. Among these mtDNA mutations, 140 and 28 mutations were detected in group A and the controls, respectively. The D-loop, CYTB and 12s rRNA were the three most common mutation regions in both groups, with significant differences between the groups observed at nucleotide positions C309CC, T489C CA514deletion, T16249C and G16474GG (D-loop); T14783C, G15043A, G15301A, and A15662G (CYTB); and G709A (12s rRNA). G15043A and A15662G had been associated with mitochondrial diseases. Our findings suggest that mtDNA mutations occur frequently in long-term ART-treated, HIV-1-infected children who have an excellent virological response, although they did not have obvious current symptoms. The CYTB region may play an important role in mtDNA mutation during ART, which might contribute to the development of subsequent mitochondrial diseases.