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

2019 ; Vol.29-11: 1852~1859

AuthorSojung Bae, Jeong Yoon Lee, Jinjong Myoung
Place of dutyKorea Zoonosis Research Institute and Genetic Engineering Research Institute, Jeonbuk National University, Jeonju 54531, Republic of Korea
TitleChikungunya Virus-Encoded nsP2, E2 and E1 Strongly Antagonize the Interferon-β Signaling Pathway
PublicationInfo J. Microbiol. Biotechnol.2019 ; Vol.29-11
AbstractChikungunya virus (CHIKV) is a single-stranded positive-sense RNA virus, belonging to the genus Alphavirus of the Togaviridae family. It causes multiple symptoms, including headache, fever, severe joint and muscle pain, and arthralgia. Since CHIKV was first isolated in Tanzania in 1952, there have been multiple outbreaks of chikungunya fever. However, its pathogenesis and mechanisms of viral immune evasion have been poorly understood. In addition, the exact roles of individual CHIKV genes on the host innate immune response remain largely unknown. To investigate if CHIKV-encoded genes modulate the type I interferon (IFN) response, each and every CHIKV gene was screened for its effects on the induction of the IFN- β promoter. Here we report that CHIKV nsP2, E2 and E1 strongly suppressed activation of the IFN-β promoter induced by the MDA5/RIG-I receptor signaling pathway, suggesting that nsP2, E2, and E1 are the major antagonists against induction of IFN-β. Delineation of underlying mechanisms of CHIKV-mediated inhibition of the IFN-β pathway may help develop virus-specific therapeutics and vaccines.
Full-Text
Key_wordChikungunya virus, interferon, antagonist
References
  1. Robinson MC. 1955. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features. Trans. R Soc. Trop. Med. Hyg. 49: 28-32.
    CrossRef
  2. Burt FJ, Rolph MS, Rulli NE, Mahalingam S, Heise MT. 2012. Chikungunya: a re-emerging virus. Lancet 379: 662-671.
    CrossRef
  3. Schwartz O, Albert ML. 2010. Biology and pathogenesis of chikungunya virus. Nat. Rev. Microbiol. 8: 491-500.
    Pubmed CrossRef
  4. Manore CA, Hickmann KS, Xu S, Wearing HJ, Hyman JM. 2014. Comparing dengue and chikungunya emergence and endemic transmission in A. aegypti and A. albopictus. J. Theor. Biol. 356: 174-191.
    Pubmed CrossRef Pubmed Central
  5. Silva LA, Dermody TS. 2017. Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies. J. Clin. Invest. 127: 737-749.
    Pubmed CrossRef Pubmed Central
  6. Gibney KB, Fischer M, Prince HE, Kramer LD, St George K, Kosoy OL, et al. 2011. Chikungunya fever in the United States:a fifteen year review of cases. Clin. Infect. Dis. 52: e121-126.
    Pubmed CrossRef
  7. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M, et al. 2007. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 370: 1840-1846.
    CrossRef
  8. Grandadam M, Caro V, Plumet S, Thiberge JM, Souares Y, Failloux AB, et al. 2011. Chikungunya virus, southeastern France. Emerg. Infect. Dis. 17: 910-913.
    Pubmed CrossRef Pubmed Central
  9. Moizeis RNC, Fernandes T, Guedes P, Pereira HWB, Lanza DCF, Azevedo JWV, et al. 2018. Chikungunya fever: a threat to global public health. Pathog. Glob. Health. 112: 182-194.
    Pubmed CrossRef Pubmed Central
  10. Law YS, U tt A, Tan YB, Zheng J, Wang S, Chen MW, et al. 2019. Structural insights into RNA recognition by the Chikungunya virus nsP2 helicase. Proc. Natl. Acad. Sci. USA 116: 9558-9567.
    Pubmed CrossRef Pubmed Central
  11. Strauss JH, Strauss EG. 1994. The alphaviruses: gene expression, replication, and evolution. Microbiol. Rev. 58: 491-562.
  12. Parashar D, Cherian S. 2014. Antiviral perspectives for chikungunya virus. Biomed. Res. Int. 2014: 631642.
    Pubmed CrossRef Pubmed Central
  13. Tuekprakhon A, Puiprom O, Sasaki T, Michiels J, Bartholomeeusen K, Nakayama EE, et al. 2018. Broadspectrum monoclonal antibodies against chikungunya virus structural proteins: Promising candidates for antibody-based rapid diagnostic test development. PLoS One 13: e0208851.
    Pubmed CrossRef Pubmed Central
  14. Snyder JE, Kulcsar KA, Schultz KL, Riley CP, Neary JT, Marr S, et al. 2013. Functional characterization of the alphavirus TF protein. J. Virol. 87: 8511-8523.
    Pubmed CrossRef Pubmed Central
  15. Kielian M, Chanel-Vos C, Liao M. 2010. Alphavirus entry and membrane fusion. Viruses. 2: 796-825.
    Pubmed CrossRef Pubmed Central
  16. Stetson DB, Medzhitov R. 2006. Type I interferons in host defense. Immunity 25: 373-381.
    Pubmed CrossRef
  17. Kang S, Myoung J. 2017. Host innate immunity against hepatitis E virus and viral evasion mechanisms. J. Microbiol. Biotechnol. 27: 1727-1735.
    Pubmed CrossRef
  18. 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.
    Pubmed CrossRef
  19. Honda K, Takaoka A, Taniguchi T. 2006. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity 25: 349-360.
    Pubmed CrossRef
  20. Akira S, Uematsu S, Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell 124: 783-801.
    Pubmed CrossRef
  21. Hu YW, Zhang J, Wu XM, Cao L, Nie P, Chang MX. 2018. TANK-binding kinase 1 (TBK1) isoforms negatively regulate Type I interferon induction by inhibiting TBK1-IRF3 interaction and IRF3 phosphorylation. Front. Immunol. 9: 84.
    Pubmed CrossRef Pubmed Central
  22. Lu LL, Puri M, Horvath CM, Sen GC. 2008. Select paramyxoviral V proteins inhibit IRF3 activation by acting as alternative substrates for inhibitor of kappaB kinase epsilon (IKKe)/TBK1. J. Biol. Chem. 283: 14269-14276.
    Pubmed CrossRef Pubmed Central
  23. Brisse M, Ly H. 2019. Comparative structure and function analysis of the RIG-I-Like rceptors: RIG-I and MDA5. Front. Immunol. 10: 1586.
    Pubmed CrossRef Pubmed Central
  24. Kang S, Choi C, Choi I, Han KN, Rho SW, Choi J, et al. 2018. Hepatitis E virus methyltransferase inhibits type I interferon induction by targeting RIG-I. J. Microbiol. Biotechnol. 28: 1554-1562.
    Pubmed CrossRef
  25. 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.
    Pubmed CrossRef
  26. Lee J, Bae S, Myoung J. 2019. Generation of full-length infectious cDNA clones of iddle east respiratory syndrome coronavirus. J. Microbiol. Biotechnol. 29: 999-1007.
    Pubmed CrossRef
  27. Lee JY, Bae S, Myoung J. 2019. Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-beta promoter activation: its implication for vaccine design. J. Microbiol. 57: 803-811.
    Pubmed CrossRef
  28. Lee JY, Bae S, Myoung J. 2019. Middle east respiratory syndrome coronavirus-encoded accessory proteins impair MDA5-and TBK1-mediated activation of NF-kappaB. J. Microbiol. Biotechnol. 29: 1316-1323.
    Pubmed CrossRef
  29. van Duijl-Richter MK, Hoornweg TE, Rodenhuis-Zybert IA, Smit JM. 2015. Early events in Chikungunya vrus infectionfrom virus cell binding to membrane fusion. Viruses 7: 3647-3674.
    Pubmed CrossRef Pubmed Central
  30. Myoung J, 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.
    Pubmed CrossRef
  31. Jang JH, Shin HW, Lee JM, Lee HW, Kim EC, Park SH. 2015. An overview of pathogen recognition receptors for innate immunity in dental pulp. Mediators Inflamm. 2015: 794143.
    Pubmed CrossRef Pubmed Central
  32. Chau TL, Gioia R, Gatot JS, Patrascu F, Carpentier I, Chapelle JP, et al. 2008. Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated? Trends Biochem. Sci. 33: 171-180.
    Pubmed CrossRef
  33. Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, et al. 2004. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc. Natl. Acad. Sci. USA 101: 17264-17269.
    Pubmed CrossRef Pubmed Central
  34. Saira K, Zhou Y, Jones C. 2007. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces degradation of interferon response factor 3 and, consequently, inhibits beta interferon promoter activity. J. Virol. 81: 3077-3086.
    Pubmed CrossRef Pubmed Central
  35. Fros JJ, Liu WJ, Prow NA, Geertsema C, Ligtenberg M, Vanlandingham DL, et al. 2010. Chikungunya virus nonstructural protein 2 inhibits type I/II interferon-stimulated JAK-STAT signaling. J. Virol. 84: 10877-10887.
    Pubmed CrossRef Pubmed Central
  36. Akhrymuk I, Kulemzin SV, Frolova EI. 2012. Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J. Virol. 86: 7180-7191.
    Pubmed CrossRef Pubmed Central
  37. Frolov I. 2004. Persistent infection and suppression of host response by alphaviruses. Arch. Virol. Suppl. 139-147.
    Pubmed CrossRef
  38. Simmons JD, White LJ, Morrison TE, Montgomery SA, Whitmore AC, Johnston RE, et al. 2009. Venezuelan equine encephalitis virus disrupts STAT1 signaling by distinct mechanisms independent of host shutoff. J. Virol. 83: 10571-10581.
    Pubmed CrossRef Pubmed Central
  39. Lei J, Hilgenfeld R. 2017. RNA-virus proteases counteracting host innate immunity. FEBS Lett. 591: 3190-3210.
    Pubmed CrossRef



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