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


Autoři: Nicola Ferreira aff001;  Christopher E. Andoniou aff003;  Kara L. Perks aff001;  Judith A. Ermer aff001;  Danielle L. Rudler aff001;  Giulia Rossetti aff001;  Ambika Periyakaruppiah aff005;  Jamie K. Y. Wong aff005;  Oliver Rackham aff001;  Peter G. Noakes aff005;  Mariapia A. Degli-Esposti aff003;  Aleksandra Filipovska aff001
Působiště autorů: Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia aff001;  Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia, Australia aff002;  Infection and Immunity Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia aff003;  Centre for Experimental Immunology, Lions Eye Institute, Perth, Western Australia, Australia aff004;  School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia aff005;  School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia aff006;  Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia aff007;  Telethon Kids Institute, QEII Medical Centre, Nedlands, Western Australia, Australia aff008;  Queensland Brain Institute, The University of Queensland, St. Lucia, Queensland, Australia aff009;  School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia aff010
Vyšlo v časopise: Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008604
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008604

Souhrn

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.

Klíčová slova:

Axons – Cytomegalovirus infection – Heart – Mitochondria – Mouse models – Respiratory infections – Viral transmission and infection – Mitochondrial diseases


Zdroje

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Genetika Reprodukční medicína

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PLOS Genetics


2020 Číslo 3

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