Short communication: transplacental nucleoside analogue exposure and mitochondrial parameters in HIV-uninfected children.

Susan B Brogly, Salvatore DiMauro, Russell B Van Dyke, Paige L Williams, Ali Naini, Daniel E Libutti, Julia Choi, Michelle Chung, Mariana Gerschenson

Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.

AIDS research and human retroviruses 2011 Jul

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Transplacental nucleoside analogue exposure can affect infant mitochondrial DNA (mtDNA). We evaluated mitochondria in peripheral blood mononuclear cells of children with and without clinical signs of mitochondrial dysfunction (MD) and antiretroviral (ARV) exposure. We previously identified 20 children with signs of MD (cases) among 1037 HIV-uninfected children born to HIV-infected women. We measured mtDNA copies/cell and oxidative phosphorylation (OXPHOS) NADH dehydrogenase (complex I) and cytochrome c oxidase (complex IV) protein levels and enzyme activities, determined mtDNA haplogroups and deletions in 18 of 20 cases with stored samples and in sex- and age-matched HIV-uninfected children, both ARV exposed and unexposed, (1) within 18 months of birth and (2) at the time of presentation of signs of MD. In specimens drawn within 18 months of birth, mtDNA levels were higher and OXPHOS protein levels and enzyme activities lower in cases than controls. In contrast, at the time of MD presentation, cases and ARV-exposed controls had lower mtDNA levels, 214 and 215 copies/cell, respectively, than ARV-unexposed controls, 254 copies/cell. OXPHOS protein levels and enzyme activities were lower in cases than exposed controls, and higher in cases than unexposed controls, except for complex IV activity, which was higher in cases. Haplotype H was less frequent among cases (6%) than controls (31%). No deletions were found. The long-term significance of these small but potentially important alterations should continue to be studied as these children enter adolescence and adulthood.

Citation

Susan B Brogly, Salvatore DiMauro, Russell B Van Dyke, Paige L Williams, Ali Naini, Daniel E Libutti, Julia Choi, Michelle Chung, Mariana Gerschenson. Short communication: transplacental nucleoside analogue exposure and mitochondrial parameters in HIV-uninfected children. AIDS research and human retroviruses. 2011 Jul;27(7):777-83