Yabo Ouyang1,2,3, Feili Wei1,2,3, Luxin Qiao1,2,3, Kai Liu1,2,3, Yaowu Dong4, Xianghua Guo1,2,3, Shanshan Wang1,2,3, Lijun Pang1,2,3, Minghua Lin1,2,3, Fujie Zhang5, Dongdong Lin1, Dexi Chen1,2,3. 1. Beijing YouAn Hospital, Capital Medical University, Beijing, China. 2. Beijing Institute of Hepatology, Beijing, China. 3. Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing, China. 4. Branch of Shang Cai, Henan province, Division of Treatment and Care, National Center for AIDS/STD Control and Prevention, Zhumadian, China. 5. Division of Treatment and Care, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Abstract
Objectives: There is growing concern about mitochondrial DNA (mtDNA) mutations with long-term NRTI exposure in HIV-1 infected children. Methods: Twenty-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. Results: The 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 and P = 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). Conclusions: Our 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.
Objectives: There is growing concern about mitochondrial DNA (mtDNA) mutations with long-term NRTI exposure in HIV-1 infectedchildren. Methods: Twenty-four HIV-1 infectedchildren 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. Results: The 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 and P = 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). Conclusions: Our findings reveal the spectrum of mtDNA variants in HIV-1-infectedchildren who had an excellent virological response. mtDNA mutations accumulated during ART may play an important role in facilitating the occurrence of mitochondrial dysfunction.
Authors: Amy S Graham; Martha J Holmes; Francesca Little; Els Dobbels; Mark F Cotton; Barbara Laughton; Andre van der Kouwe; Ernesta M Meintjes; Frances C Robertson Journal: Neuroimage Clin Date: 2020-11-19 Impact factor: 4.881
Authors: Valérie Desquiret-Dumas; Morgana D'Ottavi; Audrey Monnin; David Goudenège; Nicolas Méda; Amélie Vizeneux; Chipepo Kankasa; Thorkild Tylleskar; Céline Bris; Vincent Procaccio; Nicolas Nagot; Philippe Van de Perre; Pascal Reynier; Jean-Pierre Molès Journal: Biomedicines Date: 2022-07-25
Authors: Audrey Monnin; Valérie Desquiret-Dumas; Nicolas Méda; David Goudenège; Céline Bris; Chipepo Kankasa; Mandisa Singata-Madliki; Thorkild Tylleskar; Vincent Procaccio; Nicolas Nagot; Philippe Van de Perre; Pascal Reynier; Jean-Pierre Molès Journal: J Clin Med Date: 2021-05-28 Impact factor: 4.241