We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease.
- Authors
Ferreira, Nicola; Andoniou, Christopher E.; Perks, Kara L.; Ermer, Judith A.; Rudler, Danielle L.; Rossetti, Giulia; Periyakaruppiah, Ambika; Wong, Jamie K. Y.; Rackham, Oliver; Noakes, Peter G.; Degli-Esposti, Mariapia A.; Filipovska, Aleksandra
- 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. Author summary: Mitochondrial diseases are the most commonly inherited metabolic disorders that are heterogenic and have varied disease onset and progression. Acquired infections and the associated inflammatory responses are known triggers for mitochondrial disease in the clinic and can cause progressive deterioration in patients with mitochondrial disease. Knowledge of how an infection causes and contributes to the progression of mitochondrial disease is completely lacking and has never before been investigated. Here we examined the effects of a viral infection in a model of energy dysfunction and identified that cytomegalovirus can worsen the progression of mitochondrial disease symptoms.
- Subjects
PATHOLOGY; CYTOCHROME oxidase; SYMPTOMS; GENETIC disorders; VIRUS diseases; CYTOMEGALOVIRUS diseases
- Publication
PLoS Genetics, 2020, Vol 16, Issue 3, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1008604