PLoS Genetics (Mar 2020)

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

DOI
https://doi.org/10.1371/journal.pgen.1008604
Journal volume & issue
Vol. 16, no. 3
p. e1008604

Abstract

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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.