Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease

Nicola Ferreira, Christopher E. Andoniou, Kara L. Perks, Judith A. Ermer, Danielle L. Rudler, Giulia Rossetti, Ambika Periyakaruppiah, Jamie K.Y. Wong, Oliver Rackham, Peter G. Noakes, Mariapia A. Degli-Esposti, Aleksandra Filipovska

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Abstract

The influence of environmental insults on the onset and progression of mitochondrial diseases is unknown. To evaluate the effects of infection on mitochondrial disease we used a mouse model of Leigh Syndrome, where a missense mutation in the Taco1 gene results in the loss of the translation activator of cytochrome c oxidase subunit I (TACO1) protein. The mutation leads to an isolated complex IV deficiency that mimics the disease pathology observed in human patients with TACO1 mutations. We infected Taco1 mutant and wild-type mice with a murine cytomegalovirus and show that a common viral infection exacerbates the complex IV deficiency in a tissue-specific manner. We identified changes in neuromuscular morphology and tissue-specific regulation of the mammalian target of rapamycin pathway in response to viral infection. Taken together, we report for the first time that a common stress condition, such as viral infection, can exacerbate mitochondrial dysfunction in a genetic model of mitochondrial disease.

Original languageEnglish
Article numbere1008604
JournalPLoS Genetics
Volume16
Issue number3
DOIs
Publication statusPublished - Mar 2020

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    Ferreira, N., Andoniou, C. E., Perks, K. L., Ermer, J. A., Rudler, D. L., Rossetti, G., Periyakaruppiah, A., Wong, J. K. Y., Rackham, O., Noakes, P. G., Degli-Esposti, M. A., & Filipovska, A. (2020). Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease. PLoS Genetics, 16(3), [e1008604]. https://doi.org/10.1371/journal.pgen.1008604