Advertisement

Journal of Microbiology

, Volume 57, Issue 12, pp 1126–1131 | Cite as

Methyltransferase of a cell culture-adapted hepatitis E inhibits the MDA5 receptor signaling pathway

  • Jinjong MyoungEmail author
  • Jeong Yoon Lee
  • Kang Sang Min
Virology

Abstract

Hepatitis E virus (HEV) is a causative agent of acute hepatitis and jaundice. The number of human infections is approximated to be over 20 million cases per year. The transmission is mainly via the fecal-oral route and contaminated water and food are considered to be a major source of infection. As a mouse model is not available, a recent development of a cell culture-adapted HEV strain (47832c) is considered as a very important tools for molecular analysis of HEV pathogenesis in cells. Previously, we demonstrated that HEV-encoded methyltransferase (MeT) encoded by the 47832c strain inhibits MDA5- and RIG-I-mediated activation of interferon β (IFN-β) promoter. Here, we report that MeT impairs the phosphorylation and activation of interferon regulatory factor 3 and the p65 subunit of NF-κB in a dose-dependent manner. In addition, the MeT encoded by the 47832c, but not that of HEV clinical or field isolates (SAR-55, Mex-14, KC-1, and ZJ-1), displays the inhibitory effect. A deeper understanding of MeTmediated suppression of IFN-β expression would provide basis of the cell culture adaptation of HEV.

Keywords

hepatitis E virus methyltransferase interferon 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Education (2017R1A6A1A03015876) and by a grant from the Center for Analytical Research of Disaster Science of Korea Basic Science Institute (C38711) to J. Kwon. J. Myoung was supported by “Research Base Construction Fund Support Program” funded by Jeonbuk National University in 2019.

References

  1. Ahola, T. and Karlin, D.G. 2015. Sequence analysis reveals a conserved extension in the capping enzyme of the alphavirus supergroup, and a homologous domain in nodaviruses. Biol. Direct., 10, 16.CrossRefGoogle Scholar
  2. Akira, S., Uematsu, S., and Takeuchi, O. 2006. Pathogen recognition and innate immunity. Cell, 124, 783–801.CrossRefGoogle Scholar
  3. Denner, J. 2019. Hepatitis E virus (HEV)-The Future. Viruses, 11, 251.CrossRefGoogle Scholar
  4. Ding, Q., Heller, B., Capuccino, J.M., Song, B., Nimgaonkar, I., Hrebikova, G., Contreras, J.E., and Ploss, A. 2017. Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles. Proc. Natl. Acad. Sci. USA, 114, 1147–1152.CrossRefGoogle Scholar
  5. Fujita, T., Onoguchi, K., Onomoto, K., Hirai, R., and Yoneyama, M. 2007. Triggering antiviral response by RIG-I-related RNA helicases. Biochimie, 89, 754–760.CrossRefGoogle Scholar
  6. Hornung, V., Ellegast, J., Kim, S., Brzozka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.K., Schlee, M., et al. 2006. 5′-Triphosphate RNA is the ligand for RIG-I. Science, 314, 994–997.CrossRefGoogle Scholar
  7. Jilani, N., Das, B.C., Husain, S.A., Baweja, U.K., Chattopadhya, D., Gupta, R.K., Sardana, S., and Kar, P. 2007. Hepatitis E virus infection and fulminant hepatic failure during pregnancy. J. Gastroenterol. Hepatol., 22, 676–682.CrossRefGoogle Scholar
  8. Kanade, G.D., Pingale, K.D., and Karpe, Y.A. 2018. Activities of thrombin and factor Xa are essential for replication of hepatitis E virus and are possibly implicated in ORF1 polyprotein processing. J. Virol., 92, pii: e01853–17.CrossRefGoogle Scholar
  9. Kang, S., Choi, C., Choi, I., Han, K.N., Rho, S.W., Choi, J., Kwon, J., Park, M.K., Kim, S.J., and Myoung, J. 2018. Hepatitis E virus methyltransferase inhibits type I interferon induction by targeting RIG-I. J. Microbiol. Biotechnol., 28, 1554–1562.CrossRefGoogle Scholar
  10. Kang, S. and Myoung, J. 2017a. Host innate immunity against hepatitis E virus and viral evasion mechanisms. J. Microbiol. Biotechnol., 27, 1727–1735.CrossRefGoogle Scholar
  11. Kang, S. and Myoung, J. 2017b. Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas. J. Microbiol., 55, 319–329.CrossRefGoogle Scholar
  12. Kato, H., Takeuchi, O., Mikamo-Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T.S., Fujita, T., and Akira, S. 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.CrossRefGoogle Scholar
  13. Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K.J., et al. 2006. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature, 441, 101–105.CrossRefGoogle Scholar
  14. Kim, E. and 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.CrossRefGoogle Scholar
  15. Koonin, E.V., Gorbalenya, A.E., Purdy, M.A., Rozanov, M.N., Reyes, G.R., and Bradley, D.W. 1992. Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses. Proc. Natl. Acad. Sci. USA, 89, 8259–8263.CrossRefGoogle Scholar
  16. Lee, J., Bae, S., and Myoung, J. 2019a. Generation of full-length infectious cDNA clones of Middle East respiratory syndrome coronavirus. J. Microbiol. Biotechnol., 29, 999–1007.CrossRefGoogle Scholar
  17. Lee, J.Y., Bae, S., and Myoung, J. 2019b. Middle East respiratory syndrome coronavirus-encoded accessory proteins impair MDA5-and TBK1-mediated activation of NF-κB. J. Microbiol. Biotechnol., 29, 1316–1323.CrossRefGoogle Scholar
  18. Lee, J.Y., Bae, S., and Myoung, J. 2019c. Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design. J. Microbiol., 57, 803–811.CrossRefGoogle Scholar
  19. Loo, Y.M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., Akira, S., Gill, M.A., Garcia-Sastre, A., Katze, M.G., et al. 2008. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J. Virol., 82, 335–345.CrossRefGoogle Scholar
  20. Medzhitov, R. 2007. Recognition of microorganisms and activation of the immune response. Nature, 449, 819–826.CrossRefGoogle Scholar
  21. Myoung, J. and Min, K. 2019. Dose-dependent inhibition of melanoma differentiation-associated gene 5-mediated activation of type I interferon responses by methyltransferase of hepatitis E virus. J. Microbiol. Biotechnol., 29, 1137–1143.CrossRefGoogle Scholar
  22. Nair, V.P., Anang, S., Subramani, C., Madhvi, A., Bakshi, K., Srivastava, A., Shalimar, Nayak, B., Ranjith Kumar, C.T., and Surjit, M. 2016. Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis E virus. PLoS Pathog., 12, e1005521.CrossRefGoogle Scholar
  23. Navaneethan, U., Al Mohajer, M., and Shata, M.T. 2008. Hepatitis E and pregnancy: understanding the pathogenesis. Liver Int., 28, 1190–1199.CrossRefGoogle Scholar
  24. Park, M.K., Cho, H., Roh, S.W., Kim, S.J., and Myoung, J. 2019. Cell type-specific interferon-gamma-mediated antagonism of KSHV lytic replication. Sci. Rep., 9, 2372.CrossRefGoogle Scholar
  25. Pichlmair, A., Schulz, O., Tan, C.P., Naslund, T.I., Liljestrom, P., Weber, F., and Reis e Sousa, C. 2006. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. Science, 314, 997–1001.CrossRefGoogle Scholar
  26. Ropp, S.L., Tam, A.W., Beames, B., Purdy, M., and Frey, T.K. 2000. Expression of the hepatitis E virus ORF1. Arch. Virol., 145, 1321–1337.CrossRefGoogle Scholar
  27. Schemmerer, M., Apelt, S., Trojnar, E., Ulrich, R.G., Wenzel, J.J., and Johne, R. 2016. Enhanced replication of hepatitis E virus strain 47832c in an A549-derived subclonal cell line. Viruses, 8, pii: E267.CrossRefGoogle Scholar
  28. Shukla, P., Nguyen, H.T., Torian, U., Engle, R.E., Faulk, K., Dalton, H.R., Bendall, R.P., Keane, F.E., Purcell, R.H., and Emerson, S.U. 2011. Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant. Proc. Natl. Acad. Sci. USA, 108, 2438–2443.CrossRefGoogle Scholar
  29. Takeuchi, O. and Akira, S. 2010. Pattern recognition receptors and inflammation. Cell, 140, 805–820.CrossRefGoogle Scholar
  30. Theofilopoulos, A.N., Baccala, R., Beutler, B., and Kono, D.H. 2005. Type I interferons (alpha/beta) in immunity and autoimmunity. Annu. Rev. Immunol., 23, 307–336.CrossRefGoogle Scholar
  31. Xi, Y., Day, S.L., Jackson, R.J., and Ranasinghe, C. 2012. Role of novel type I interferon epsilon in viral infection and mucosal immunity. Mucosal Immunol., 5, 610–622.CrossRefGoogle Scholar

Copyright information

© The Microbiological Society of Korea 2019

Authors and Affiliations

  • Jinjong Myoung
    • 1
    Email author
  • Jeong Yoon Lee
    • 1
  • Kang Sang Min
    • 1
  1. 1.Korea Zoonosis Research Institute, Genetic Engineering Research Institute and Department of Bioactive Material ScienceJeonbuk National UniversityJeonjuRepublic of Korea

Personalised recommendations