Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy

作者：E. Arnaudo, Sarah Shanske, S. DiMauro, E.A. Schon, E.A. Schon, Carlos T. Moraes, Eric A. Schon, E.A. Schon, Marinos C. Dalakas · 发表于：The Lancet · 年份：1991 · DOI：10.1016/0140-6736(91)91294-5 · 被引用次数：506 · 研究领域：Metabolism and Genetic Disorders、HIV/AIDS drug development and treatment、Mitochondrial Function and Pathology

Long-term zidovudine therapy in patients with human immunodeficiency virus (HIV) infection can cause a destructive mitochondrial myopathy with histological features of ragged-red fibres (RRF) and proliferation of abnormal mitochondria. In 9 zidovudine-treated patients with this myopathy we found severely reduced amounts (up to 78% reduction vs normal adult controls) of mitochondrial DNA (mtDNA) in muscle biopsy specimens by means of Southern blotting. In 2 HIV-positive patients who had not received zidovudine, muscle mtDNA content did not differ from that in the 4 controls. Depletion of mtDNA seems to be reversible, since 1 patient showed a substantial reduction in RRF and a concomitant pronounced increase in muscle mtDNA content after zidovudine therapy was discontinued. Depletion of muscle mtDNA is probably due to zidovudine-induced inhibition of mtDNA replication by DNA polymerase gamma and is not a secondary effect of HIV infection.