Journal of Microbiology and Biotechnology
The Korean Society for Microbiology and Biotechnology publishes the Journal of Microbiology and Biotechnology.

2019 ; Vol.29-7: 1137~1143

AuthorJinjong Myoung, Kang Sang Min
Place of dutyKorea Zoonosis Research Institute and Genetic Engineering Research Institute, Chonbuk National University, Jeonju 54896, Republic of Korea
TitleDose-Dependent Inhibition of Melanoma Differentiation-Associated Gene 5-Mediated Activation of Type I Interferon Responses by Methyltransferase of Hepatitis E Virus
PublicationInfo J. Microbiol. Biotechnol.2019 ; Vol.29-7
AbstractHepatitis E virus (HEV) accounts for 20 million infections in humans worldwide. In most cases, the infections are self-limiting while HEV genotype 1 infection cases may lead to lethal infections in pregnant women (~ 20% fatality). The lack of small animal models has hampered detailed analysis of virus-host interactions and HEV-induced pathology. Here, by employing a recently developed culture-adapted HEV, we demonstrated that methyltransferase, a nonstructural protein, strongly inhibits melanoma differentiation-associated gene 5 (MDA5)- mediated activation of type I interferon responses. Compared to uninfected controls, HEVinfected cells display significantly lower levels of IFN-β promoter activation when assessed by luciferase assay and RT-PCR. HEV genome-wide screening showed that HEV-encoded methyltransferase (MeT) strongly inhibits MDA5-mediated transcriptional activation of IFN-β and NF-κB in a dose-responsive manner whether or not it is expressed in the presence/ absence of a tag fused to it. Taken together, current studies clearly demonstrated that HEV MeT is a novel antagonist of MDA5-mediated induction of IFN-β signaling.
Full-Text
Key_wordHepatitis E virus, interferon beta, methyltransferase
References
  1. Denner J. 2019. Hepatitis E virus (HEV)-the future. Viruses 11(3) pii: E251.
  2. Berke T, Matson DO. 2000. Reclassification of the Caliciviridae into distinct genera and exclusion of hepatitis E virus from the family on the basis of comparative phylogenetic analysis. Arch. Virol. 145: 1421-1436.
  3. Kang HS, Myoung J, So EY, Bahk YY, Kim BS. 2016. Transgenic expression of non-structural genes of Theiler’s virus suppresses initial viral replication and pathogenesis of demyelination. J. Neuroinflammation 13: 133.
  4. Kang S, Myoung J. 2017. Host innate immunity against hepatitis E virus and viral evasion mechanisms. J. Microbiol. Biotechnol. 27: 1727-1735.
  5. Purdy MA, Khudyakov YE. 2010. Evolutionary history and population dynamics of hepatitis E virus. PLoS One 5:e14376.
  6. Jilani N, Das BC, Husain SA, Baweja UK, Chattopadhya D, Gupta RK, et al. 2007. Hepatitis E virus infection and fulminant hepatic failure during pregnancy. J. Gastroenterol. Hepatol. 22: 676-682.
  7. Navaneethan U, Al Mohajer M, Shata MT. 2008. Hepatitis E and pregnancy: understanding the pathogenesis. Liver Int. 28: 1190-1199.
  8. Ifeorah IM, Faleye TOC, Bakarey AS, Adewumi MO, Akere A, Omoruyi EC, et al. 2017. Acute hepatitis E virus infection in two geographical regions of nigeria. J. Pathog. 2017: 4067108.
  9. Bazerbachi F, Haffar S, Garg SK, Lake JR. 2016. Extrahepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature. Gastroenterol. Rep. (Oxf) 4: 1-15.
  10. Guthmann JP, Klovstad H, Boccia D, Hamid N, Pinoges L, Nizou JY, et al. 2006. A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods. Clin. Infect. Dis. 42: 1685-1691.
  11. Howard C M, H andzel T , Hill V R, G rytdal S P, B lanton C , Kamili S, et al. 2010. Novel risk factors associated with hepatitis E virus infection in a large outbreak in northern Uganda: results from a case-control study and environmental analysis. Am. J. Trop. Med. Hyg. 83: 1170-1173.
  12. Lhomme S, Abravanel F, Dubois M, Sandres-Saune K, Rostaing L, Kamar N, et al. 2012. Hepatitis E virus quasispecies and the outcome of acute hepatitis E in solidorgan transplant patients. J. Virol. 86: 10006-10014.
  13. Lhomme S, Marion O, Abravanel F, Chapuy-Regaud S, Kamar N, Izopet J. 2016. Hepatitis E pathogenesis. Viruses 8.
  14. Akira S, Uematsu S, Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell 124: 783-801.
  15. Kang S, Myoung J. 2017. Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas. J. Microbiol. 55: 319-329.
  16. Medzhitov R. 2007. Recognition of microorganisms and activation of the immune response. Nature 449: 819-826.
  17. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, et al. 2008. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J. Virol. 82:335-345.
  18. Takeuchi O, Akira S. 2010. Pattern recognition receptors and inflammation. Cell 140: 805-820.
  19. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, et al. 2006. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441: 101-105.
  20. Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, et al. 2006. 5’-Triphosphate RNA is the ligand for RIG-I. Science 314: 994-997.
  21. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, et al. 2006. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates. Science 314:997-1001.
  22. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. 2004. The RNA helicase RIG-I has an essential function in double-stranded RNAinduced innate antiviral responses. Nat. Immunol. 5: 730-737.
  23. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, et al. 2005. IPS-1, an adaptor triggering RIG-I- and Mda5mediated type I interferon induction. Nat. Immunol. 6: 981-988.
  24. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, et al. 2005. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437: 1167-1172.
  25. Seth RB, Sun L, Ea CK, Chen ZJ. 2005. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122: 669-682.
  26. Kang S, C hoi C, C hoi I, H an KN, Rho SW, C hoi J, et al. 2018. Hepatitis E virus methyltransferase inhibits type I interferon induction by targeting RIG-I. J. Microbiol. Biotechnol. 28: 1554-1562.
  27. Marques JT, Devosse T, Wang D, Zamanian-Daryoush M, Serbinowski P, Hartmann R, et al. 2006. A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells. Nat. Biotechnol. 24: 559-565.
  28. Saito T, Owen DM, Jiang F, Marcotrigiano J, Gale M, Jr. 2008. Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature 454: 523-527.
  29. Poeck H, Bscheider M, Gross O, Finger K, Roth S, Rebsamen M, et al. 2010. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat. Immunol. 11: 63-69.
  30. Schlee M, Roth A, Hornung V, Hagmann CA, Wimmenauer V, Barchet W, et al. 2009. Recognition of 5’ triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity 31: 25-34.
  31. Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, et al. 2008. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J. Exp. Med. 205: 1601-1610.
  32. Johne R, Trojnar E, Filter M, Hofmann J. 2016. Thermal stability of hepatitis E virus as estimated by a cell culture method. Appl. Environ. Microbiol. 82: 4225-4231.
  33. Schemmerer M, Apelt S, Trojnar E, Ulrich RG, Wenzel JJ, Johne R. 2016. Enhanced replication of hepatitis E virus strain 47832c in an A549-derived subclonal cell line. Viruses 8.
  34. Kou Y, Wan M, Shi W, Liu J, Zhao Z, Xu Y, et al. 2018. Performance of homologous and heterologous prime-boost immunization regimens of recombinant adenovirus and modified vaccinia virus ankara expressing an Ag85B-TB10.4 fusion protein against mycobacterium tuberculosis. J. Microbiol. Biotechnol. 28: 1022-1029.
  35. Phuong NH, Kwak C , Heo C K, C ho EW, Y ang J, P oo H. 2018. Development and characterization of monoclonal antibodies against nucleoprotein for diagnosis of influenza A virus. J. Microbiol. Biotechnol. 28: 809-815.
  36. Kim E, Myoung J. 2018. Hepatitis E virus papain-like cysteine protease inhibits type I interferon induction by down-regulating melanoma differentiation-associated gene 5. J. Microbiol. Biotechnol. 28: 1908-1915.
  37. Park MK, Cho H, Roh SW, Kim SJ, Myoung J. 2019. Cell type-specific interferon-gamma-mediated antagonism of KSHV lytic replication. Sci. Rep. 9: 2372.
  38. Baek YH, Cheon HS, Park SJ, Lloren KKS, Ahn SJ, Jeong JH, et al. 2018. Simple, rapid and sensitive portable molecular diagnosis of SFTS virus using reverse transcriptional loopmediated isothermal amplification (RT-LAMP). J. Microbiol. Biotechnol. 28: 1928-1936.
  39. Dai W, Wu Y, Bi J, Wang J, Wang S, Kong W, et al. 2018. Antiviral effect of retro-2.1 against herpes simplex virus type 2 in vitro. J. Microbiol. Biotechnol. 28: 849-859.
  40. Karpe YA, Lole KS. 2011. Deubiquitination activity associated with hepatitis E virus putative papain-like cysteine protease. J. Gen. Virol. 92: 2088-2092.
  41. Oshiumi H, Miyashita M, Matsumoto M, Seya T. 2013. A distinct role of riplet-mediated K63-linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses. PLoS Pathog. 9: e1003533.
  42. Nan Y, Yu Y, Ma Z, Khattar SK, Fredericksen B, Zhang YJ. 2014. Hepatitis E virus inhibits type I interferon induction by ORF1 products. J. Virol. 88: 11924-11932.



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