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

PLoS Genet. 2020 Mar 4;16(3):e1008604. doi: 10.1371/journal.pgen.1008604. eCollection 2020 Mar.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome-c Oxidase Deficiency / genetics*
  • Cytochrome-c Oxidase Deficiency / virology
  • Cytomegalovirus Infections / genetics*
  • Cytomegalovirus Infections / virology
  • Disease Models, Animal
  • Electron Transport Complex IV / genetics*
  • Leigh Disease / genetics
  • Leigh Disease / virology
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / virology
  • Mitochondrial Proteins / genetics*
  • Muromegalovirus / pathogenicity*
  • Mutation / genetics
  • TOR Serine-Threonine Kinases / genetics


  • Mitochondrial Proteins
  • Electron Transport Complex IV
  • TOR Serine-Threonine Kinases

Grants and funding

This project was supported by fellowships and project grants from the National Health and Medical Research Council (APP1058442, APP1045677, APP1041582, APP1023460, APP1005030, APP1043978 to AF and OR, APP1119298 and APP1071822 to MADE), Australian Research Council (to AF and OR), the Cancer Council of Western Australia (to OR and AF). PGN was supported by a MNDRIA grant-in aid. NF was supported by a UWA Australian Postgraduate Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.