1887

Abstract

Enterovirus 71 (EVA71), a virus of the genus Enterovirus in the family Picornaviridae, is one of the main causative agents of hand, foot and mouth disease in infected infants and young children. In this study, we report that cells with EVA71 infection exhibit increased levels of cytochrome c release and caspase-3 activation. EVA71 infection induces the conformational activation of pro-apoptotic protein Bax and the subsequent formation of oligomers of Bax in mitochondria. Inhibitors that block caspase-8 activation cannot inhibit apoptosis induced by EVA71 infection. Importantly, cells with Bax but not Bak or caspase-8 knockdown show resistance to apoptosis induced by EVA71 infection. Mitochondria isolated from EVA71-infected cells display clear Bax-binding ability and the subsequent release of cytochrome c. Therefore, these results indicate that EVA71 infection directly impacts the mitochondrial apoptotic pathway by modulating the recruitment and activation of Bax.

Keyword(s): apoptosis , Bax and enterovirus 71
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2017-04-01
2019-09-18
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References

  1. Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2001;292:727–730 [CrossRef][PubMed]
    [Google Scholar]
  2. Brenner C, Kroemer G. Apoptosis. Mitochondria – the death signal integrators. Science 2000;289:1150–1151 [CrossRef][PubMed]
    [Google Scholar]
  3. Willis SN, Chen L, Dewson G, Wei A, Naik E et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-XL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev 2005;19:1294–1305 [CrossRef][PubMed]
    [Google Scholar]
  4. Kim H, Tu HC, Ren D, Takeuchi O, Jeffers JR et al. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol Cell 2009;36:487–499 [CrossRef][PubMed]
    [Google Scholar]
  5. Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW et al. BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis.. Mol Cell 2001;8:705–711 [CrossRef][PubMed]
    [Google Scholar]
  6. Joza N, Susin SA, Daugas E, Stanford WL, Cho SK et al. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 2001;410:549–554 [CrossRef][PubMed]
    [Google Scholar]
  7. Degenhardt K, Sundararajan R, Lindsten T, Thompson C, White E, Bax WE. Bax and Bak independently promote cytochrome c release from mitochondria. J Biol Chem 2002;277:14127–14134 [CrossRef][PubMed]
    [Google Scholar]
  8. Yamaguchi R, Lartigue L, Perkins G, Scott RT, Dixit A et al. Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization. Mol Cell 2008;31:557–569 [CrossRef][PubMed]
    [Google Scholar]
  9. Dewson G, Kluck RM. Mechanisms by which Bak and Bax permeabilise mitochondria during apoptosis. J Cell Sci 2009;122:2801–2808 [CrossRef][PubMed]
    [Google Scholar]
  10. Zhou L, Chang DC. Dynamics and structure of the Bax-Bak complex responsible for releasing mitochondrial proteins during apoptosis. J Cell Sci 2008;121:2186–2196 [CrossRef][PubMed]
    [Google Scholar]
  11. Mullauer FB, Kessler JH, Medema JP. Betulinic acid induces cytochrome c release and apoptosis in a Bax/Bak-independent, permeability transition pore dependent fashion. Apoptosis 2009;14:191–202 [CrossRef][PubMed]
    [Google Scholar]
  12. Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ et al. Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci USA 1998;95:14681–14686 [CrossRef]
    [Google Scholar]
  13. Hamacher-Brady A, Brady NR. Bax/Bak-dependent, Drp1-independent targeting of X-linked inhibitor of apoptosis protein (XIAP) into inner mitochondrial compartments counteracts Smac/DIABLO-dependent effector caspase activation. J Biol Chem 2015;290:22005–22018 [CrossRef][PubMed]
    [Google Scholar]
  14. Tolskaya EA, Romanova LI, Kolesnikova MS, Ivannikova TA, Smirnova EA et al. Apoptosis-inducing and apoptosis-preventing functions of poliovirus. J Virol 1995;69:1181–1189[PubMed]
    [Google Scholar]
  15. Stewart SA, Poon B, Jowett JB, Chen IS. Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest. J Virol 1997;71:5579–5592[PubMed]
    [Google Scholar]
  16. Nomura-Takigawa Y, Nagano-Fujii M, Deng L, Kitazawa S, Ishido S et al. Non-structural protein 4A of hepatitis C virus accumulates on mitochondria and renders the cells prone to undergoing mitochondria-mediated apoptosis. J Gen Virol 2006;87:1935–1945 [CrossRef][PubMed]
    [Google Scholar]
  17. Schaecher SR, Touchette E, Schriewer J, Buller RM, Pekosz A. Severe acute respiratory syndrome coronavirus gene 7 products contribute to virus-induced apoptosis. J Virol 2007;81:11054–11068 [CrossRef][PubMed]
    [Google Scholar]
  18. Liang CC, Sun MJ, Lei HY, Chen SH, Yu CK et al. Human endothelial cell activation and apoptosis induced by enterovirus 71 infection. J Med Virol 2004;74:597–603 [CrossRef][PubMed]
    [Google Scholar]
  19. Cheng EH, Levine B, Boise LH, Thompson CB, Hardwick JM. Bax-independent inhibition of apoptosis by Bcl-XL. Nature 1996;379:554–556 [CrossRef][PubMed]
    [Google Scholar]
  20. Cong HL, Ning D, Tian HC, Yang Y, Zhang W et al. Enterovirus 71 VP1 activates calmodulin-dependent protein kinase II and results in the rearrangement of vimentin in human astrocyte cells. Plos One 2013;8:
    [Google Scholar]
  21. Lee MS, Lin TY, Chiang PS, Li WC, Luo ST et al. An investigation of epidemic enterovirus 71 infection in Taiwan, 2008: clinical, virologic, and serologic features. Pediatr Infect Dis J 2010;29:1030–1034 [CrossRef][PubMed]
    [Google Scholar]
  22. Chang SC, Lin JY, Lo LY, Li ML, Shih SR. Diverse apoptotic pathways in enterovirus 71-infected cells. J Neurovirol 2004;10:338–349 [CrossRef][PubMed]
    [Google Scholar]
  23. Blondel B, Colbere-Garapin F, Couderc T, Wirotius A, Guivel-Benhassine F. Poliovirus, pathogenesis of poliomyelitis, and apoptosis. Curr Top Microbiol 2005;289:25–56
    [Google Scholar]
  24. Ammendolia MG, Tinari A, Calcabrini A, Superti F. Poliovirus infection induces apoptosis in CaCo-2 cells. J Med Virol 1999;59:122–129 [CrossRef][PubMed]
    [Google Scholar]
  25. Han B, Jf X, Chen YF, Gao L, Cy M. The influence of carvedilol on apoptosis and expression of Bcl-2/Bax protein of cultured cardiomyocytes infected by coxsackievirus B3. Eur Heart J 2010;31:476
    [Google Scholar]
  26. Feuer R, Mena I, Pagarigan RR, Harkins S, Hassett DE et al. Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am J Pathol 2003;163:1379–1393 [CrossRef][PubMed]
    [Google Scholar]
  27. Gullberg M, Tolf C, Jonsson N, Polacek C, Precechtelova J et al. A single coxsackievirus B2 capsid residue controls cytolysis and apoptosis in rhabdomyosarcoma cells. J Virol 2010;84:5868–5879 [CrossRef][PubMed]
    [Google Scholar]
  28. Liu J, Wei T, Kwang J. Avian encephalomyelitis virus induces apoptosis via major structural protein VP3. Virology 2002;300:39–49 [CrossRef][PubMed]
    [Google Scholar]
  29. Autret A, Martin-Latil S, Mousson L, Wirotius A, Petit F et al. Poliovirus induces Bax-dependent cell death mediated by c-Jun NH2-terminal kinase. J Virol 2007;81:7504–7516 [CrossRef][PubMed]
    [Google Scholar]
  30. Du N, Cong H, Tian H, Zhang H, Zhang W et al. Cell surface vimentin is an attachment receptor for enterovirus 71. J Virol 2014;88:5816–5833 [CrossRef][PubMed]
    [Google Scholar]
  31. Marshall WL, Yim C, Gustafson E, Graf T, Sage DR et al. Epstein-Barr virus encodes a novel homolog of the bcl-2 oncogene that inhibits apoptosis and associates with Bax and Bak. J Virol 1999;73:5181–5185[PubMed]
    [Google Scholar]
  32. Douglas AE, Corbett KD, Berger JM, Mcfadden G, Handel TM. Structure of M11L: a myxoma virus structural homolog of the apoptosis inhibitor, Bcl-2. Protein Sci 2007;16:695–703 [CrossRef][PubMed]
    [Google Scholar]
  33. Sundararajan R, Cuconati A, Nelson D, White E. Tumor necrosis factor-alpha induces Bax-Bak interaction and apoptosis, which is inhibited by adenovirus E1B 19K. J Biol Chem 2001;276:45120–45127 [CrossRef][PubMed]
    [Google Scholar]
  34. Gregorczyk KP, Wvzewski Z, Szulc-Dabrowska L, Niemialtowski M. Inhibition of mitochondrial pathway of apoptosis by poxvirus proteins. Med Weter 2014;70:456–459
    [Google Scholar]
  35. Couderc T, Guivel-Benhassine F, Calaora V, Gosselin AS, Blondel B. An ex vivo murine model to study poliovirus-induced apoptosis in nerve cells. J Gen Virol 2002;83:1925–1930 [CrossRef][PubMed]
    [Google Scholar]
  36. Girard S, Couderc T, Destombes J, Thiesson D, Delpeyroux F et al. Poliovirus induces apoptosis in the mouse central nervous system. J Virol 1999;73:6066–6072[PubMed]
    [Google Scholar]
  37. Wang SM, Liu CC, Tseng HW, Wang JR, Huang CC et al. Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications. Clin Infect Dis 1999;29:184–190 [CrossRef][PubMed]
    [Google Scholar]
  38. Li J, Chen F, Liu T, Wang L. MRI findings of neurological complications in hand-foot-mouth disease by enterovirus 71 infection. Int J Neurosci 2012;122:338–344 [CrossRef][PubMed]
    [Google Scholar]
  39. Xie Z, Schendel S, Matsuyama S, Reed JC. Acidic pH promotes dimerization of Bcl-2 family proteins. Biochemistry 1998;37:6410–6418 [CrossRef][PubMed]
    [Google Scholar]
  40. Sarosiek KA, Chi X, Bachman JA, Sims JJ, Montero J et al. BID preferentially activates BAK while BIM preferentially activates BAX, affecting chemotherapy response. Mol Cell 2013;51:751–765 [CrossRef][PubMed]
    [Google Scholar]
  41. Jurgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D et al. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci USA 1998;95:4997–5002 [CrossRef]
    [Google Scholar]
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