Journal of Microbiology

, Volume 57, Issue 9, pp 803–811 | Cite as

Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design

  • Jeong Yoon Lee
  • Sojung Bae
  • Jinjong MyoungEmail author
Microbial Pathogenesis and Host-Microbe Interaction


Middle East respiratory syndrome coronavirus (MERS-CoV) is a causative agent of severe-to-fatal pneumonia especially in patients with pre-existing conditions, such as smoking and chronic obstructive pulmonary disease (COPD). MERS-CoV transmission continues to be reported in the Saudi Arabian Peninsula since its discovery in 2012. However, it has rarely been epidemic outside the area except one large outbreak in South Korea in May 2015. The genome of the epidemic MERS-CoV isolated from a Korean patient revealed its homology to previously reported strains. MERS-CoV encodes 5 accessory proteins and generally, they do not participate in the genome transcription and replication but rather are involved in viral evasion of the host innate immune responses. Here we report that ORF8b, an accessory protein of MERS-CoV, strongly inhibits both MDA5- and RIG-I-mediated activation of interferon beta promoter activity while downstream signaling molecules were left largely unaffected. Of note, MDA5 protein levels were significantly down-regulated by ORF8b and co-expression of ORF4a and ORF4b. These novel findings will facilitate elucidation of mechanisms of virus-encoded evasion strategies, thus helping design rationale antiviral countermeasures against deadly MERS-CoV infection.


accessory protein interferon beta MERS-CoV ORF8b 


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This research was supported by HI15C3039 through the Korea Health Industry Development Institute (KHIDI) funded by the Korean Ministry of Health and Welfare.


  1. Abdul-Rasool, S. and Fielding, B.C. 2010. Understanding human coronavirus HCoV-NL63. Open Virol. J. 4, 76–84.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Akira, S., Uematsu, S., and Takeuchi, O. 2006. Pathogen recognition and innate immunity. Cell 124, 783–801.CrossRefPubMedGoogle Scholar
  3. Alraddadi, B.M., Watson, J.T., Almarashi, A., Abedi, G.R., Turkistani, A., Sadran, M., Housa, A., Almazroa, M.A., Alraihan, N., Banjar, A., et al. 2016. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg. Infect. Dis. 22, 49–55.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Banerjee, A., Falzarano, D., Rapin, N., Lew, J., and Misra, V. 2019. Interferon regulatory factor 3-mediated signaling limits Middle-East respiratory syndrome (MERS) coronavirus propagation in cells from an insectivorous bat. Viruses 11, 152.CrossRefPubMedCentralGoogle Scholar
  5. Bradburne, A.F., Bynoe, M.L., and Tyrrell, D.A. 1967. Effects of a “new” human respiratory virus in volunteers. Br. Med. J. 3, 767–769.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Cardenas, W.B., Loo, Y.M., Gale, M.Jr., Hartman, A.L., Kimberlin, C.R., Martinez-Sobrido, L., Saphire, E.O., and Basler, C.F. 2006. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J. Virol. 80, 5168–5178.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chan, J.F., Lau, S.K., To, K.K., Cheng, V.C., Woo, P.C., and Yuen, K.Y. 2015. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin. Microbiol. Rev. 28, 465–522.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chan, C.P., Yuen, C.K., Cheung, P.H., Fung, S.Y., Lui, P.Y., Chen, H., Kok, K.H., and Jin, D.Y. 2018. Antiviral activity of double-stranded RNA-binding protein PACT against influenza A virus mediated via suppression of viral RNA polymerase. FASEB J. 32, 4380–4393.CrossRefPubMedGoogle Scholar
  9. Chau, T.L., Gioia, R., Gatot, J.S., Patrascu, F., Carpentier, I., Chapelle, J.P., O’Neill, L., Beyaert, R., Piette, J., and Chariot, A. 2008. Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated? Trends Biochem. Sci. 33, 171–180.CrossRefPubMedGoogle Scholar
  10. Cho, M. and Myoung, J. 2015. OX40 and 4-1BB downregulate Kaposi’s sarcoma-associated herpesvirus replication in lymphatic endothelial cells, but 4-1BB and not OX40 inhibits viral replication in B-cells. J. Gen. Virol. 96, 3635–3645.CrossRefPubMedGoogle Scholar
  11. Chowell, G., Abdirizak, F., Lee, S., Lee, J., Jung, E., Nishiura, H., and Viboud, C. 2015. Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study. BMC Med. 13, 210.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Clement, J.F., Meloche, S., and Servant, M.J. 2008. The IKK-related kinases: from innate immunity to oncogenesis. Cell Res. 18, 889–899.CrossRefPubMedGoogle Scholar
  13. Comar, C.E., Goldstein, S.A., Li, Y., Yount, B., Baric, R.S., and Weiss, S.R. 2019. Antagonism of dsRNA-induced innate immune pathways by NS4a and NS4b accessory proteins during MERS coronavirus infection. mBio 10, e00319–19.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Corman, V.M., Eckerle, I., Bleicker, T., Zaki, A., Landt, O., Eschbach-Bludau, M., evan Boheemen, S., Gopal, R., Ballhause, M., Bestebroer, T.M., et al. 2012. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill. 17, pii:20285.Google Scholar
  15. Fehr, A.R. and Perlman, S. 2015. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol. Biol. 1282, 1–23.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Fitzgerald, K.A., McWhirter, S.M., Faia, K.L., Rowe, D.C., Latz, E., Golenbock, D.T., Coyle, A.J., Liao, S.M., and Maniatis, T. 2003. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4, 491–496.CrossRefPubMedGoogle Scholar
  17. Fung, I.C., Tse, Z.T., Chan, B.S., and Fu, K.W. 2015. Middle East respiratory syndrome in the Republic of Korea: transparency and communication are key. Western Pac. Surveill. Response J. 6, 1–2.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Gatot, J.S., Gioia, R., Chau, T.L., Patrascu, F., Warnier, M., Close, P., Chapelle, J.P., Muraille, E., Brown, K., Siebenlist, U., et al. 2007. Lipopolysaccharide-mediated interferon regulatory factor activation involves TBK1-IKKepsilon-dependent Lys(63)-linked polyubiquitination and phosphorylation of TANK/I-TRAF. J. Biol. Chem. 282, 31131–31146.CrossRefPubMedGoogle Scholar
  19. Goldstein, S.A. and Weiss, S.R. 2017. Origins and pathogenesis of Middle East respiratory syndrome-associated coronavirus: recent advances. F1000Res 6, 1628.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Gosert, R., Kanjanahaluethai, A., Egger, D., Bienz, K., and Baker, S.C. 2002. RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J. Virol. 76, 3697–3708.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Goubau, D., Schlee, M., Deddouche, S., Pruijssers, A.J., Zillinger, T., Goldeck, M., Schuberth, C., Van der Veen, A.G., Fujimura, T., Rehwinkel, J., et al. 2014. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5′-diphosphates. Nature 514, 372–375.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Grandvaux, N., Servant, M.J., tenOever, B., Sen, G.C., Balachandran, S., Barber, G.N., Lin, R., and Hiscott, J. 2002. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J. Virol. 76, 5532–5539.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Ha, S., Choi, I.S., Choi, C., and Myoung, J. 2016. Infection models of human norovirus: challenges and recent progress. Arch. Virol. 161, 779–788.CrossRefPubMedGoogle Scholar
  24. Hacker, H. and Karin, M. 2006. Regulation and function of IKK and IKK-related kinases. Sci. STKE 2006, re13.CrossRefPubMedGoogle Scholar
  25. Hamre, D. and Procknow, J.J. 1966. A new virus isolated from the human respiratory tract. Proc. Soc. Exp. Biol. Med. 121, 190–193.CrossRefPubMedGoogle Scholar
  26. Hayman, D.T. 2016. Bats as viral reservoirs. Annu. Rev. Virol. 3, 77–99.CrossRefPubMedGoogle Scholar
  27. Ho, T.H., Kew, C., Lui, P.Y., Chan, C.P., Satoh, T., Akira, S., Jin, D.Y., and Kok, K.H. 2016. PACT- and RIG-I-dependent activation of type I interferon production by a defective interfering RNA derived from measles virus vaccine. J. Virol. 90, 1557–1568.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Honda, K., Takaoka, A., and Taniguchi, T. 2006. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity 25, 349–360.CrossRefPubMedGoogle Scholar
  29. Honda, K. and Taniguchi, T. 2006. IRFs: master regulators of signalling by toll-like receptors and cytosolic pattern-recognition receptors. Nat. Rev. Immunol. 6, 644–658.CrossRefPubMedGoogle Scholar
  30. Islam, M.N., Lee, K.W., Yim, H.S., Lee, S.H., Jung, H.C., Lee, J.H., and Jeong, J.Y. 2017. Optimizing T4 DNA polymerase conditions enhances the efficiency of one-step sequence- and ligation-independent cloning. Biotechniques 63, 125–130.CrossRefPubMedGoogle Scholar
  31. Jeong, J.Y., Yim, H.S., Ryu, J.Y., Lee, H.S., Lee, J.H., Seen, D.S., and Kang, S.G. 2012. One-step sequence- and ligation-independent cloning as a rapid and versatile cloning method for functional genomics studies. Appl. Environ. Microbiol. 78, 5440–5443.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. Kang, S. and Myoung, J. 2017a. Host innate immunity against hepatitis E virus and viral evasion mechanisms. J. Microbiol. Biotechnol. 27, 1727–1735.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. Kang, H.S., Myoung, J., So, E.Y., Bahk, Y.Y., and Kim, B.S. 2016. Transgenic expression of non-structural genes of Theiler’s virus suppresses initial viral replication and pathogenesis of demyelination. J. Neuroinflammation 13, 133.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K.J., Takeuchi, O., and Akira, S. 2005. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat. Immunol. 6, 981–988.CrossRefPubMedGoogle Scholar
  37. Kew, C., Lui, P.Y., Chan, C.P., Liu, X., Au, S.W., Mohr, I., Jin, D.Y., and Kok, K.H. 2013. Suppression of PACT-induced type I interferon production by herpes simplex virus 1 Us11 protein. J. Virol. 87, 13141–13149.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Ki, M. 2015. 2015 MERS outbreak in Korea: hospital-to-hospital transmission. Epidemiol. Health 37, e2015033.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Kim, Y.J., Cho, Y.J., Kim, D.W., Yang, J.S., Kim, H., Park, S., Han, Y.W., Yun, M.R., Lee, H.S., Kim, A.R., et al. 2015. Complete genome sequence of Middle East respiratory syndrome coronavirus KOR/KNIH/002_05_2015, isolated in South Korea. Genome Announc. 3, e00787–15.PubMedPubMedCentralGoogle Scholar
  40. 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.CrossRefPubMedGoogle Scholar
  41. Kim, K.H., Tandi, T.E., Choi, J.W., Moon, J.M., and Kim, M.S. 2017. Middle East respiratory syndrome coronavirus (MERSCoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications. J. Hosp. Infect. 95, 207–213.CrossRefPubMedGoogle Scholar
  42. Kindler, E., Thiel, V., and Weber, F. 2016. Interaction of SARS and MERS coronaviruses with the antiviral interferon response. Adv. Virus Res. 96, 219–243.CrossRefPubMedGoogle Scholar
  43. Kok, K.H., Lui, P.Y., Ng, M.H., Siu, K.L., Au, S.W., and Jin, D.Y. 2011. The double-stranded RNA-binding protein PACT functions as a cellular activator of RIG-I to facilitate innate antiviral response. Cell Host Microbe 9, 299–309.CrossRefPubMedGoogle Scholar
  44. Ksiazek, T.G., Erdman, D., Goldsmith, C.S., Zaki, S.R., Peret, T., Emery, S., Tong, S., Urbani, C., Comer, J.A., Lim, W., et al. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348, 1953–1966.CrossRefPubMedGoogle Scholar
  45. Lau, S.K., Woo, P.C., Yip, C.C., Tse, H., Tsoi, H.W., Cheng, V.C., Lee, P., Tang, B.S., Cheung, C.H., Lee, R.A., et al. 2006. Coronavirus HKU1 and other coronavirus infections in Hong Kong. J. Clin. Microbiol. 44, 2063–2071.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Lee, J.Y., Lee, J.S., Materne, E.C., Rajala, R., Ismail, A.M., Seto, D., Dyer, D.W., Rajaiya, J., and Chodosh, J. 2018. Bacterial RecA protein promotes adenoviral recombination during in vitro infection. mSphere 3, e00105–18.PubMedPubMedCentralGoogle Scholar
  47. Li, W., Shi, Z., Yu, M., Ren, W., Smith, C., Epstein, J.H., Wang, H., Crameri, G., Hu, Z., Zhang, H., et al. 2005. Bats are natural reservoirs of SARS-like coronaviruses. Science 310, 676–679.CrossRefPubMedGoogle Scholar
  48. Lim, P.L. 2015. Middle East respiratory syndrome (MERS) in Asia: lessons gleaned from the South Korean outbreak. Trans. R. Soc. Trop. Med. Hyg. 109, 541–542.CrossRefPubMedGoogle Scholar
  49. Liu, S., Cai, X., Wu, J., Cong, Q., Chen, X., Li, T., Du, F., Ren, J., Wu, Y.T., Grishin, N.V., et al. 2015. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 347, aaa2630.CrossRefPubMedGoogle Scholar
  50. Lui, P.Y., Wong, L.R., Ho, T.H., Au, S.W.N., Chan, C.P., Kok, K.H., and Jin, D.Y. 2017. PACT facilitates RNA-induced activation of MDA5 by promoting MDA5 oligomerization. J. Immunol. 199, 1846–1855.CrossRefPubMedGoogle Scholar
  51. Lundin, A., Dijkman, R., Bergstrom, T., Kann, N., Adamiak, B., Hannoun, C., Kindler, E., Jonsdottir, H.R., Muth, D., Kint, J., et al. 2014. Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the Middle East respiratory syndrome virus. PLoS Pathog. 10, e1004166.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Luthra, P., Sun, D., Silverman, R.H., and He, B. 2011. Activation of IFN-β expression by a viral mRNA through RNase L and MDA5. Proc. Natl. Acad. Sci. USA 108, 2118–2123.CrossRefPubMedGoogle Scholar
  53. Malathi, K., Dong, B., Gale, M.Jr., and Silverman, R.H. 2007. Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448, 816–819.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Matthews, K.L., Coleman, C.M., van der Meer, Y., Snijder, E.J., and Frieman, M.B. 2014. The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling. J. Gen. Virol. 95, 874–882.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Maxmen, A. 2017. Bats are global reservoir for deadly coronaviruses. Nature 546, 340.CrossRefPubMedGoogle Scholar
  56. Medzhitov, R. 2007. Recognition of microorganisms and activation of the immune response. Nature 449, 819–826.CrossRefPubMedGoogle Scholar
  57. Meyerholz, D.K., Lambertz, A.M., and McCray, P.B.Jr. 2016. Dipeptidyl peptidase 4 distribution in the human respiratory tract: Implications for the Middle East respiratory syndrome. Am. J. Pathol. 186, 78–86.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., and Tschopp, J. 2005. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437, 1167–1172.CrossRefPubMedGoogle Scholar
  59. Motz, C., Schuhmann, K.M., Kirchhofer, A., Moldt, M., Witte, G., Conzelmann, K.K., and Hopfner, K.P. 2013. Paramyxovirus V proteins disrupt the fold of the RNA sensor MDA5 to inhibit antiviral signaling. Science 339, 690–693.CrossRefPubMedGoogle Scholar
  60. Nam, H.S., Park, J.W., Ki, M., Yeon, M.Y., Kim, J., and Kim, S.W. 2017. High fatality rates and associated factors in two hospital outbreaks of MERS in Daejeon, the Republic of Korea. Int. J. Infect. Dis. 58, 37–42.CrossRefPubMedGoogle Scholar
  61. Niemeyer, D., Zillinger, T., Muth, D., Zielecki, F., Horvath, G., Suliman, T., Barchet, W., Weber, F., Drosten, C., and Muller, M.A. 2013. Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist. J. Virol. 87, 12489–12495.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Oh, M.D. 2016. The Korean Middle East respiratory syndrome coronavirus outbreak and our responsibility to the global scientific community. Infect. Chemother. 48, 145–146.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Park, Y.S., Lee, C., Kim, K.M., Kim, S.W., Lee, K.J., Ahn, J., and Ki, M. 2015. The first case of the 2015 Korean Middle East respiratory syndrome outbreak. Epidemiol. Health 37, e2015049.CrossRefPubMedPubMedCentralGoogle Scholar
  65. Prins, K.C., Cardenas, W.B., and Basler, C.F. 2009. Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1. J. Virol. 83, 3069–3077.CrossRefPubMedPubMedCentralGoogle Scholar
  66. Prins, K.C., Delpeut, S., Leung, D.W., Reynard, O., Volchkova, V.A., Reid, S.P., Ramanan, P., Cardenas, W.B., Amarasinghe, G.K., Volchkov, V.E., et al. 2010. Mutations abrogating VP35 interaction with double-stranded RNA render Ebola virus avirulent in guinea pigs. J. Virol. 84, 3004–3015.CrossRefPubMedPubMedCentralGoogle Scholar
  67. Rota, P.A., Oberste, M.S., Monroe, S.S., Nix, W.A., Campagnoli, R., Icenogle, J.P., Penaranda, S., Bankamp, B., Maher, K., Chen, M.H., et al. 2003. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300, 1394–1399.CrossRefPubMedGoogle Scholar
  68. Runge, S., Sparrer, K.M., Lassig, C., Hembach, K., Baum, A., Garcia-Sastre, A., Soding, J., Conzelmann, K.K., and Hopfner, K.P. 2014. In vivo ligands of MDA5 and RIG-I in measles virus-infected cells. PLoS Pathog. 10, e1004081.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Seth, R.B., Sun, L., Ea, C.K., and Chen, Z.J. 2005. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122, 669–682.CrossRefPubMedGoogle Scholar
  70. Seys, L.J.M., Widagdo, W., Verhamme, F.M., Kleinjan, A., Janssens, W., Joos, G.F., Bracke, K.R., Haagmans, B.L., and Brusselle, G.G. 2018. DPP4, the Middle East respiratory syndrome coronavirus receptor, is upregulated in lungs of smokers and chronic obstructive pulmonary disease patients. Clin. Infect. Dis. 66, 45–53.CrossRefPubMedGoogle Scholar
  71. Siu, K.L., Yeung, M.L., Kok, K.H., Yuen, K.S., Kew, C., Lui, P.Y., Chan, C.P., Tse, H., Woo, P.C., Yuen, K.Y., et al. 2014. Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response. J. Virol. 88, 4866–4876.CrossRefPubMedPubMedCentralGoogle Scholar
  72. Tyrrell, D.A. and Bynoe, M.L. 1965. Cultivation of a novel type of common-cold virus in organ cultures. Br. Med. J. 1, 1467–1470.CrossRefPubMedPubMedCentralGoogle Scholar
  73. Vabret, A., Dina, J., Gouarin, S., Petitjean, J., Corbet, S., and Freymuth, F. 2006. Detection of the new human coronavirus HKU1: a report of 6 cases. Clin. Infect. Dis. 42, 634–639.CrossRefPubMedGoogle Scholar
  74. van Boheemen, S., de Graaf, M., Lauber, C., Bestebroer, T.M., Raj, V.S., Zaki, A.M., Osterhaus, A.D.M.E., Haagmans, B.L., Gorbalenya, A.E., Snijder, E.J., et al. 2012. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio 3, e00473–12.CrossRefPubMedPubMedCentralGoogle Scholar
  75. van den Brand, J.M., Smits, S.L., and Haagmans, B.L. 2015. Pathogenesis of Middle East respiratory syndrome coronavirus. J. Pathol. 235, 175–184.CrossRefPubMedGoogle Scholar
  76. van der Hoek, L., Pyrc, K., Jebbink, M.F., Vermeulen-Oost, W., Berkhout, R.J., Wolthers, K.C., Wertheim-van Dillen, P.M., Kaandorp, J., Spaargaren, J., and Berkhout, B. 2004. Identification of a new human coronavirus. Nat. Med. 10, 368–373.CrossRefPubMedGoogle Scholar
  77. Versteeg, G.A., Bredenbeek, P.J., van den Worm, S.H., and Spaan, W.J. 2007. Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition. Virology 361, 18–26.CrossRefPubMedGoogle Scholar
  78. Weber, F., Wagner, V., Rasmussen, S.B., Hartmann, R., and Paludan, S.R. 2006. Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J. Virol. 80, 5059–5064.CrossRefPubMedPubMedCentralGoogle Scholar
  79. Widagdo, W., Sooksawasdi Na Ayudhya, S., Hundie, G.B., and Haagmans, B.L. 2019. Host determinants of MERS-CoV transmission and pathogenesis. Viruses 11, 280.CrossRefPubMedCentralGoogle Scholar
  80. Woo, P.C., Lau, S.K., Chu, C.M., Chan, K.H., Tsoi, H.W., Huang, Y., Wong, B.H., Poon, R.W., Cai, J.J., Luk, W.K., et al. 2005a. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J. Virol. 79, 884–895.CrossRefPubMedPubMedCentralGoogle Scholar
  81. Woo, P.C., Lau, S.K., Tsoi, H.W., Huang, Y., Poon, R.W., Chu, C.M., Lee, R.A., Luk, W.K., Wong, G.K., Wong, B.H., et al. 2005b. Clinical and molecular epidemiological features of coronavirus HKU1-associated community-acquired pneumonia. J. Infect. Dis. 192, 1898–1907.CrossRefPubMedGoogle Scholar
  82. Yang, Y., Ye, F., Zhu, N., Wang, W., Deng, Y., Zhao, Z., and Tan, W. 2015. Middle East respiratory syndrome coronavirus ORF 4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets. Sci. Rep. 5, 17554.CrossRefPubMedPubMedCentralGoogle Scholar
  83. Yang, Y., Zhang, L., Geng, H., Deng, Y., Huang, B., Guo, Y., Zhao, Z., and Tan, W. 2013. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell 4, 951–961.CrossRefPubMedPubMedCentralGoogle Scholar
  84. Yip, C.W., Hon, C.C., Shi, M., Lam, T.T., Chow, K.Y., Zeng, F., and Leung, F.C. 2009. Phylogenetic perspectives on the epidemiology and origins of SARS and SARS-like coronaviruses. Infect. Genet. Evol. 9, 1185–1196.CrossRefPubMedGoogle Scholar
  85. Zaki, A.M., van Boheemen, S., Bestebroer, T.M., Osterhaus, A.D.M.E., and Fouchier, R.A.M. 2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367, 1814–1820.CrossRefPubMedGoogle Scholar
  86. Zhou, P., Fan, H., Lan, T., Yang, X.L., Shi, W.F., Zhang, W., Zhu, Y., Zhang, Y.W., Xie, Q.M., Mani, S., et al. 2018. Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 556, 255–258.CrossRefPubMedGoogle Scholar
  87. Zhou, H. and Perlman, S. 2007. Mouse hepatitis virus does not induce Beta interferon synthesis and does not inhibit its induction by double-stranded RNA. J. Virol. 81, 568–574.CrossRefPubMedGoogle Scholar
  88. Zielecki, F., Weber, M., Eickmann, M., Spiegelberg, L., Zaki, A.M., Matrosovich, M., Becker, S., and Weber, F. 2013. Human cell tropism and innate immune system interactions of human respiratory coronavirus EMC compared to those of severe acute respiratory syndrome coronavirus. J. Virol. 87, 5300–5304.CrossRefPubMedPubMedCentralGoogle Scholar
  89. Zust, R., Cervantes-Barragan, L., Habjan, M., Maier, R., Neuman, B.W., Ziebuhr, J., Szretter, K.J., Baker, S.C., Barchet, W., Diamond, M.S., et al. 2011. Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat. Immunol. 12, 137–143.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Microbiological Society of Korea 2019

Authors and Affiliations

  1. 1.Korea Zoonosis Research Institute, Genetic Engineering Research Institute & Department of Bioactive Material Science, College of Natural ScienceChonbuk National UniversityJeonjuRepublic of Korea

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