ХАРАКТЕРИСТИКА ВИРУСА ЭНЦЕФАЛОМИОКАРДИТА И ЕГО ЗООНОЗНЫЙ ПОТЕНЦИАЛ (ОБЗОР ЛИТЕРАТУРЫ). ЧАСТЬ II. ПАТОГЕНЕЗ. КРУГ ВОСПРИИМЧИВЫХ ОРГАНИЗМОВ

Среди факторов вирулентности ЭМКВ в литературе выделяют как непосредственное действие вирусных белков (В2*, L, 2A), так и воспалительную реакцию организма. В зависимости от штамма ЭМКВ и вида инфицированного животного существуют особенности в выраженности и характере клинических проявлений заболевания. Также установлены различия патогенетических механизмов тканевых поражений в зависимости от величины инфицирующей дозы вируса, как, например, при развитии ЭМКВ-индуцированного диабета. Действие вируса in vivo изучалось на примерах свиней, грызунов и обезьян. Круг поражаемых животных весьма широк, а инфекция распространена практически повсеместно. В том числе немало работ описывает достаточно высокую иммунологическую прослойку среди людей, а также вспышки заболеваний среди населения. Таким образом, ЭМКВ представляет опасность не только для зоопарков и приматологических центров, но имеет явный зоонозный потенциал.

1. Carocci M., Bakkali-Kassimi L. The encephalomyocarditis virus. Virulence. 2012; 3 (4): 351–367. DOI: 10.4161/viru.20573

2. Loughran G., Firth A.E., Atkins J.F. Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the cardiovirus genome. Proc. Natl. Acad. Sci. USA. 2011; 108(46): E1111–E1119. DOI: 10.1073/pnas.1102932108

3. Balvay L., Soto Rifo R., Ricci E.P., Decimo D., Ohlmann T. Structural and functional diversity of viral IRESes. Biochim. Biophys. Acta. 2009; 1789(9-10): 542–557. DOI: 10.1016/j.bbagrm.2009.07.005

4. Papon L., Oteiza A., Imaizumi T., Kato H., Brocchi E., Lawson T.G., Akira S., Mechti N. The viral RNA recognition sensor RIG-I is degraded during encephalomyocarditis virus (EMCV) infection. Virology. 2009; 393(2): 311–318. DOI: 10.1016/j.virol.2009.08.009

5. de Jong A.S., de Mattia F., Van Dommelen M.M., Lanke K., Melchers W.J., Willems P.H., van Kuppeveld F.J. Functional analysis of picornavirus 2B proteins: effects on calcium homeostasis and intracellular protein traffcking. J. Virol. 2008; 82(7): 3782–3790. DOI: 10.1128/JVI.02076-07

6. Choe S.S., Dodd D.A., Kirkegaard K. Inhibition of cellular protein secretion by picornaviral 3A proteins. Virology. 2005; 337(1): 18–29. DOI: 10.1016/j.virol.2005.03.036

7. Moffat K., Knox C., Howell G., Clark S.J., Yang H., Belsham G.J., Ryan М., Wileman Т. Inhibition of the secretory pathway by foot-and-mouth disease virus 2BC protein is reproduced by coexpression of 2B with 2C, and the site of inhibition is determined by the subcellular location of 2C. J. Virol. 2007; 81(3): 1129–1139. DOI: 10.1128/JVI.00393-06

8. Canelli E., Luppi A., Lavazza A., Lelli D., Sozzi E., Martin A.M., Gelmetti D., Pascotto E., Sandri C., Magnone W., Cordioli P. Encephalomyocarditis virus infection in an Italian zoo. Virol. J. 2010; 7: 64. DOI: 10.1186/1743-422X-7-64

9. Czechowicz J., Huaman J.L., Forshey B.M., Morrison A.C., Castillo R., Huaman A., Caceda R., Eza D., Rocha C., Blair P.J., Olson J.G., Kochel T.J. Prevalence and risk factors for encephalomyocarditis virus infection in Peru. Vector. Borne. Zoonotic. Dis. 2011; 11(4): 367–374. DOI: 10.1089/vbz.2010.0029

10. Oberste M.S., Gotuzzo E., Blair P., Nix W.A., Ksiazek T.G., Comer J.A., Rollin Р., Goldsmith С.S., Olson J., Koche T.J. Human febrile illness caused by encephalomyocarditis virus infection, Peru. Emerg. Infect. Dis. 2009; 15(4): 640–646. DOI: 10.3201/eid1504.081428

11. An D.-J., Jeong W., Jeoung H.-Y., Yoon S.H., Kim H.J., Choi C.U., Park B.K. Encephalomyocarditis in Korea: serological survey in pigs and phylogenetic analysis of two historical isolates. Vet. Microbiol. 2009; 137(1–2): 37–44. DOI: 10.1016/j.vetmic.2009.01.005

12. Ge X., Zhao D., Liu C., Wang F., Guo X, Yang H. Seroprevalence of encephalomyocarditis virus in intensive pig farms in China. Vet. Rec. 2010; 166(5): 145–146. DOI: 10.1136/vr.b4766

13. Billinis C. Encephalomyocarditis virus infection in wildlife species in Greece. J. Wildl. Dis. 2009; 45(2): 522–526.

14. Psalla D., Psychas V., Spyrou V., Billinis C., Papaioannou N., Vlemmas I. Pathogenesis of experimental encephalomyocarditis: a histopathological, immunohistochemical and virological study in rats. J. Comp. Pathol. 2006; 134(1): 30–39. DOI: 10.1016/j.jcpa.2005.06.008

15. Spyrou V., Maurice H., Billinis C., Papanastassopoulou M., Psalla D., Nielen M. Transmission and pathogenicity of encephalomyocarditis virus (EMCV) among rats. Vet. Res. 2004; 35(1): 113–122. DOI: 10.1051/vetres:2003044

16. Kluivers M., Maurice H., Vyt P., Koenen F., Nielen M. Transmission of encephalomyocarditis virus in pigs estimated from feld data in Belgium by means of R0. Vet Res. 2006; 37(6): 757–766. DOI: 10.1051/vetres:2006035

17. Koenen F. Chapter 17: Encephalomyocarditis Virus. In: Straw B.E., D’Allaire S., Zimmerman J.J., Taylor D.J, editors. Disease of the Swine. 9th ed. Boston: Blackwell Science; 2006.

18. Juncker-Voss M., Prosl H., Lussy H., Enzenberg U., Auer H., Lassnig H., Müller M., Nowotny N. Screening for antibodies against zoonotic agents among employees of the Zoological Garden of Vienna, Schönbrunn, Austria. Berl. Munch. Tierarztl. Wochenschr. 2004; 117(9–10): 404–409.

19. Masek-Hammerman K., Miller A.D., Lin K.C., MacKey J., Weissenböck H., Gierbolini L., Burgos A., Perez H., Mansfeld K.G. Epizootic myocarditis associated with encephalomyocarditis virus in a group of rhesus macaques (Macaca mulatta). Vet. Pathol. 2012; 49(2): 386–392. DOI: 10.1177/0300985811409254

20. Gelmetti D., Meroni A., Brocchi E., Koenen F., Cammarata G. Pathogenesis of encephalomyocarditis experimental infection in young piglets: a potential animal model to study viral myocarditis. Vet Res. 2006; 37(1): 15–23. DOI: 10.1051/vetres:2005041

21. Psalla D., Psychas V., Spyrou V., Billinis C., Papaioannou N., Vlemmas I. Pathogenesis of experimental encephalomyocarditis: a histopathological, immunohistochemical and virological study in mice. J. Comp. Pathol. 2006; 135(2–3): 142–145. DOI: 10.1016/j.jcpa.2006.04.003

22. Yoon J.-W., Jun H.-S. Viruses cause type 1 diabetes in animals. Ann. NY Acad. Sci. 2006; 1079(1): 138–146. DOI: 10.1196/annals.1375.021

23. Nakayama Y., Su W., Ohguchi A., Nakayama H., Doi K. Experimental encephalomyocarditis virus infection in pregnant mice. Exp. Mol. Pathol. 2004; 77(2): 133–137. DOI: 10.1016/j.yexmp.2004.02.003

24. Yamanouchi-Ueno A., Nakayama Y., Doi K. Characteristics of testicular lesions in mice infected with a low dose of encephalomyocarditis (EMC) virus. Exp. Mol. Pathol. 2004; 77(2): 72–76. DOi: 10.1016/j.yexmp.2003.12.008

25. Doi K. Experimental encephalomyocarditis virus infection in small laboratory rodents. J. Comp. Pathol. 2011; 144(1): 25–40. DOI: 10.1016/j.jcpa.2010.05.001

26. Matsumori A., Yamamoto K., Shimada M. Cetirizine a histamine H1 receptor antagonist improves viral myocarditis. J. Inflamm. (Lond). 2010; 7: 39. DOI: 10.1186/1476-9255-7-39

27. Wang J.-F., Meissner A., Malek S., Chen Y., Ke Q., Zhang J., Chu V., Hampton T.G., Crumpacker C.S., Abelmann W.H., Amende I., Morgan J.P. Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis. Am. J. Physiol. Heart Circ. Physiol. 2005; 289(4): H1577–1583. DOI: 10.1152/ajpheart.00258.2005

28. Matsumori A., Nunokawa Y., Yamaki A., Yamamoto K., Hwang M.W., Miyamoto T., Hara M., Nishio R., Kitaura-Inenaga K., Ono K. Suppression of cytokines and nitric oxide production, and protection against lethal endotoxemia and viral myocarditis by a new NF-kappaB inhibitor. Eur. J. Heart. Fail. 2004; 6(2): 137–144. DOI: 10.1016/j.ejheart.2003.10.007

29. Nasu-Nishimura Y., Taniuchi Y., Nishimura T., Sakudo A., Nakajima K., Ano Y., Sugiura K., Sakaguchi S., Itohara S., Onodera T. Cellular prion protein prevents brain damage after encephalomyocarditis virus infection in mice. Arch. Virol. 2008; 153(6): 1007–1012. DOI: 10.1007/s00705-008-0086-x

30. Takeda M., Ohtsuka R., Nakayama Y., Doi K. The role of CD4(+) T cells in biphasic hind limb paralysis induced by the D variant of encephalomyocarditis virus (EMC-D) in DBA/2 mice. Exp. Anim. 2004; 53(1): 31–35.

31. Ano Y., Sakudo A., Kimata T., Uraki R., Sugiura K., Onodera T. Oxidative damage to neurons caused by the induction of microglial NADPH oxidase in encephalomyocarditis virus infection. Neurosci. Lett. 2010; 469(1): 39–43. DOI: 10.1016/j.neulet.2009.11.040

32. Bardina M.V., Lidsky P.V., Sheval E.V., Fominykh K.V., van Kuppeveld F.J., Polyakov V.Y., Agol V.I. Mengovirus-induced rearrangement of the nuclear pore complex: hijacking cellular phosphorylation machinery. J. Virol. 2009; 83(7): 3150–3161. DOI: 10.1128/JVI.01456-08

33. Porter F.W., Brown B., Palmenberg A.C. Nucleoporin phosphorylation triggered by the encephalomyocarditis virus leader protein is mediated by mitogen-activated protein kinases. J. Virol. 2010; 84(24): 12538–12548. DOI: 10.1128/JVI.01484-09

34. Porter F.W., Palmenberg A.C. Leader-induced phosphorylation of nucleoporins correlates with nuclear traffcking inhibition by cardioviruses. J. Virol. 2009; 83(4): 1941–1951. DOI: 10.1128/JVI.01752-08

35. Porter F.W., Bochkov Y.A., Albee A.J., Wiese C., Palmenberg A.C. A picornavirus protein interacts with Ran-GTPase and disrupts nucleocytoplasmic transport. Proc. Natl. Acad. Sci. USA. 2006; 103(33): 12417–12422. DOI: 10.1073/pnas.0605375103

36. Borghese F., Michiels T. The leader protein of cardioviruses inhibits stress granule assembly. J. Virol. 2011; 85(18): 9614–9622. DOI: 10.1128/JVI.00480-11

37. Okuwa T., Taniura N., Saito M., Himeda T., Ohara Y. Opposite effects of two nonstructural proteins of Theiler’s murine encephalomyelitis virus regulates apoptotic cell death in BHK-21 cells. Microbiol. Immunol. 2010; 54(10): 639–643. DOI: 10.1111/j.1348-0421.2010.00260.x

38. Groppo R., Palmenberg A.C. Cardiovirus 2A protein associates with 40S but not 80S ribosome subunits during infection. J. Virol. 2007; 81(23): 13067–13074. DOI: 10.1128/JVI.00185-07

39. Groppo R., Brown B.A, Palmenberg A.C. Mutational analysis of the EMCV 2A protein identifes a nuclear localization signal and an eIF4E binding site. Virology. 2011; 410(1): 257–267. DOI: 10.1016/j.virol.2010.11.002

40. Ohguchi A., Nakayama Y., Yasoshima A., Doi C., Mikami T., Uetsuka K., Doi K. Encepalomyocarditis virus-induced apoptosis and ultrastructural changes in the lacrimal and parotid glands of mice. Exp. Mol. Pathol. 2006; 80(2): 201–207. DOI: 10.1016/j.yexmp.2005.06.003

41. Buenz E.J., Sauer B.M., Lafrance-Corey R.G., Deb C., Denic A., German C.L., Howe C.L. Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection. Am. J. Pathol. 2009; 175(2): 668–684. DOI: 10.2353/ajpath.2009.081126

42. Roos F.C., Roberts A.M, Hwang I.I.L, Moriyama E.H, Evans A.J., Sybingco S., Watson I.R., Carneiro L.A., Gedye C., Girardin S.E., Ailles L.E., Jewett M.A., Milosevic M., Wilson B.C., Bell J.C., Der S.D., Ohh M. Oncolytic targeting of renal cell carcinoma via encephalomyocarditis virus. EMBO Mol. Med. 2010; 2(7): 275–288. DOI: 10.1002/emmm.201000081

43. Christmann B.S., Moran J.M., McGraw J.A., Buller R.M.L., Corbett J.A. Ccr5 Regulates Inflammatory Gene Expression in Response to Encephalomyocarditis Virus Infection. Am. J. Pathol. 2011; 179(6): 2941–2951. DOI: 10.1016/j.ajpath.2011.08.012

44. Luo Y.K., Liang L., Tang Q.H., Zhou L., Shi L.J., Cong Y.Y., Lin W.C., Cui S.J. Isolation and characterization of encephalomyocarditis virus from dogs in China Sci. Rep. 2017; 7(1): 438. DOI: 10.1038/s41598-017-00435-x

45. Maurice H., Nielen M., Brocchi E., Nowotny N., Kassimi L.B., Billinis C. The occurrence of encephalomyocarditis virus (EMCV) in European pigs from 1990 to 2001. Epidemiol. Infect. 2005; 133(3): 547–557. DOI: 10.1017/S0950268804003668

46. Higuchi H., Hara M., Yamamoto K., Miyamoto T., Kinoshita M., Yamada T., Uchiyama K., Matsumori A. Mast cells play a critical role in the pathogenesis of viral myocarditis. Circulation. 2008; 118(4): 363–372. DOI: 10.1161/CIRCULATIONAHA.107.741595

47. Onodera T., Yoon J.W., Brown K.S., Notkina A.L. Evidence for a single locus controlling susceptibility to virus-induced diabetes mellitus. Nature. 1978; 274: 693–696. DOI: 10.1038/274693a0

48. Aminev A.G., Amineva S.P., Palmenberg A.C. Encephalomyocarditis viral protein 2A localizes to nucleoli and inhibits cap-dependent mRNA translation. Virus. Res. 2003; 95(1–2): 45–57. DOI: 10.1016/S0168-1702(03)00162-X

49. Martin L.R., Neal Z.C., McBride M.S., Palmenberg A.C. Mengovirus and encephalomyocarditis virus poly(C) tract lengths can affect virus growth in murine cell culture. J. Virol. 2000; 74(7): 3074–3081. DOI: 10.1128/JVI.74.7.3074-3081.2000

50. Banerjee R., Tsai W., Kim W., Dasgupta A. Interaction

51. of poliovirus-encoded 2C/2BC polypeptides with the

52. ′ terminus negative-strand cloverleaf requires an

53. intact stem-loop b. Virology. 2001; 280 (1):41–51.

54. DOI: 10.1006/viro.2000.0770

55. Helwig F.C., Schmidt C.H. A flter-passing agent

56. producing interstitial myocarditis in anthropoid apes

57. and small animals. Science. 1945; 102(2637): 31–33.

58. DOI: 10.1126/science.102.2637.31

59. Dea S., Bilodeau R., Sauvageau R., Martineau G.P.

60. Outbreaks in Quebec pig farms of respiratory and

61. reproductive problems associated with encephalomyocarditis virus. J. Vet. Diagn. Invest. 1991; 3(4):

62. –282. DOI: 10.1177/104063879100300401