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:
https://doi.org/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
1. Gorman GS, Chinnery PF, Dimauro S, Hirano M, Koga Y, McFarland R, et al. Mitochondrial diseases. Nat Rev Dis Primers. 2016;2: 16080–22. doi: 10.1038/nrdp.2016.80 27775730
2. Vafai SB, Mootha VK. Mitochondrial disorders as windows into an ancient organelle. Nature. 2012;491: 374–383. doi: 10.1038/nature11707 23151580
3. Weraarpachai W, Antonicka H, Sasarman F, Seeger J, Schrank B, Kolesar JE, et al. Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome. Nat Genet. 2009;41: 833–837. doi: 10.1038/ng.390 19503089
4. Richman TR, Spåhr H, Ermer JA, Davies SMK, Viola HM, Bates KA, et al. Loss of the RNA-binding protein TACO1 causes late-onset mitochondrial dysfunction in mice. Nat Comms. 2016;7: 11884. doi: 10.1038/ncomms11884 27319982
5. Scalzo AA, Corbett AJ, Rawlinson WD, Scott GM, Degli-Esposti MA. The interplay between host and viral factors in shaping the outcome of cytomegalovirus infection. Immunol Cell Biol. 2007;85: 46–54. doi: 10.1038/sj.icb.7100013 17146464
6. Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature. 2013;493: 338–345. doi: 10.1038/nature11861 23325216
7. Kudchodkar SB, Yu Y, Maguire TG, Alwine JC. Human cytomegalovirus infection induces rapamycin-insensitive phosphorylation of downstream effectors of mTOR kinase. J Virol. 2004;78: 11030–11039. doi: 10.1128/JVI.78.20.11030-11039.2004 15452223
8. Clippinger AJ, Maguire TG, Alwine JC. Human cytomegalovirus infection maintains mTOR activity and its perinuclear localization during amino acid deprivation. J Virol. 2011;85: 9369–9376. doi: 10.1128/JVI.05102-11 21734039
9. So E, Mitchell JC, Memmi C, Chennell G, Vizcay-Barrena G, Allison L, et al. Mitochondrial abnormalities and disruption of the neuromuscular junction precede the clinical phenotype and motor neuron loss in hFUSWT transgenic mice. Hum Mol Genet. 2018;27: 463–474. doi: 10.1093/hmg/ddx415 29194538
10. Perks KL, Ferreira N, Richman TR, Ermer JA, Kuznetsova I, Shearwood A-MJ, et al. Adult-onset obesity is triggered by impaired mitochondrial gene expression. Sci Adv. 2017;3: e1700677. doi: 10.1126/sciadv.1700677 28835921
11. Ferreira N, Perks KL, Rossetti G, Rudler DL, Hughes LA, Ermer JA, et al. Stress signaling and cellular proliferation reverse the effects of mitochondrial mistranslation. EMBO J. 2019;313: e102155. doi: 10.15252/embj.2019102155 31721250
12. Munger J, Bajad SU, Coller HA, Shenk T, Rabinowitz JD. Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog. 2006;2: e132. doi: 10.1371/journal.ppat.0020132 17173481
13. Vastag L, Koyuncu E, Grady SL, Shenk TE, Rabinowitz JD. Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. Lagunoff M, editor. PLoS Pathog. 2011;7: e1002124. doi: 10.1371/journal.ppat.1002124 21779165
14. Yu Y, Clippinger AJ, Alwine JC. Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol. 2011;19: 360–367. doi: 10.1016/j.tim.2011.04.002 21570293
15. Johnson SC, Yanos ME, Kayser EB, Quintana A, Sangesland M, Castanza A, et al. mTOR Inhibition Alleviates Mitochondrial Disease in a Mouse Model of Leigh Syndrome. Science. 2013;342: 1524–1528. doi: 10.1126/science.1244360 24231806
16. Morita M, Gravel S-P, Chénard V, Sikström K, Zheng L, Alain T, et al. mTORC1 Controls Mitochondrial Activity and Biogenesis through 4E-BP-Dependent Translational Regulation. Cell Metab. 2013;18: 698–711. doi: 10.1016/j.cmet.2013.10.001 24206664
17. Arsham AM, Howell JJ, Simon MC. A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J Biochem. 2003;278: 29655–29660. doi: 10.1074/jbc.M212770200 12777372
18. Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 2010;40: 310–322. doi: 10.1016/j.molcel.2010.09.026 20965424
19. Kudchodkar SB, Yu Y, Maguire TG, Alwine JC. Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes. Proc Natl Acad Sci U S A. 2006;103: 14182–14187. doi: 10.1073/pnas.0605825103 16959881
20. Slavuljica I, Kveštak D, Huszthy PC, Kosmac K, Britt WJ, Jonjić S. Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model. Cell Mol Immunol. 2015;12: 180–191. doi: 10.1038/cmi.2014.51 25042632
21. Tsutsui Y, Kosugi I, Kawasaki H. Neuropathogenesis in cytomegalovirus infection: indication of the mechanisms using mouse models. Rev Med Virol. 2005;15: 327–345. doi: 10.1002/rmv.475 16100703
22. Kramer T, Enquist LW. Alphaherpesvirus infection disrupts mitochondrial transport in neurons. Cell Host Microbe. 2012;11: 504–514. doi: 10.1016/j.chom.2012.03.005 22607803
23. Ong ML, Wikstrom ME, Fleming P, Estcourt MJ, Hertzog PJ, Hill GR, et al. CpG pretreatment enhances antiviral T-cell immunity against cytomegalovirus. Blood. 2013;122: 55–60. doi: 10.1182/blood-2012-12-471227 23673858
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