Browse > Article
http://dx.doi.org/10.4014/jmb.1911.11024

Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors by a Differential Mechanism  

Lee, Jeong Yoon (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Chonbuk National University)
Kim, Seong-Jun (Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology)
Myoung, Jinjong (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Chonbuk National University)
Publication Information
Journal of Microbiology and Biotechnology / v.29, no.12, 2019 , pp. 2014-2021 More about this Journal
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the genus Betacoronavirus and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such as chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-β) promoter activities. Here, we report that ORF8b seemed to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. In addition, ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, the last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/RIG-I receptor signaling pathway.
Keywords
MERS-CoV; interferon; RIG-I;
Citations & Related Records
Times Cited By KSCI : 11  (Citation Analysis)
연도 인용수 순위
1 Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, et al. 2005. IPS-1, an adaptor triggering RIG-I- and Mda5- mediated type I interferon induction. Nat. Immunol. 6: 981-988.   DOI
2 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.   DOI
3 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.   DOI
4 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.   DOI
5 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.   DOI
6 Chau TL, Gioia R, Gatot JS, Patrascu F, Carpentier I, Chapelle JP, et al. 2008. Are the IKKs and I KK-related kinases TBK1 and IKK-epsilon similarly activated? Trends Biochem. Sci. 33: 171-180.   DOI
7 Clement JF, Meloche S, Servant MJ. 2008. The IKK-related kinases: from innate immunity to oncogenesis. Cell Res. 18: 889-899.   DOI
8 Medzhitov R. 2007. Recognition of microorganisms and activation of the immune response. Nature 449: 819-826.   DOI
9 Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, et al. 2003. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4: 491-496.   DOI
10 Gatot JS, Gioia R, Chau TL, Patrascu F, Warnier M, Close P, 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.   DOI
11 Hacker H, Karin M. 2006. Regulation and function of IKK and IKK-related kinases. Sci. STKE. 2006: re13.
12 Grandvaux N, Servant MJ, tenOever B, Sen GC, Balachandran S, Barber GN, et al. 2002. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J. Virol. 76: 5532-5539.   DOI
13 Honda K, Taniguchi T. 2006. IRFs: master regulators of signalling by Toll-like receptors and cytosolic patternrecognition receptors. Nat. Rev. Immunol. 6: 644-658.   DOI
14 Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, et al. 2015. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 347: aaa2630.   DOI
15 Hiscott J, Grandvaux N, Sharma S, Tenoever BR, Servant MJ, Lin R. 2003. Convergence of the NF-kappaB and interferon signaling pathways in the regulation of antiviral defense and apoptosis. Ann. NY Acad. Sci. 1010: 237-248.   DOI
16 Wang J, Basagoudanavar SH, Wang X, Hopewell E, Albrecht R, Garcia-Sastre A, et al. 2010. NF-kappa B RelA subunit is crucial for early IFN-beta expression and resistance to RNA virus replication. J. Immunol. 185: 1720-1729.   DOI
17 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.   DOI
18 Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. 2015. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin. Microbiol. Rev. 28: 465-522.   DOI
19 Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. 2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367: 1814-1820.   DOI
20 Corman VM, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M, et al. 2012. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill. 17(39). pii: 20285.
21 Lee J, Bae S, Myoung J. 2019. Generation of full-length infectious cDNA clones of middle east respiratory syndrome coronavirus. J. Microbiol. Biotechnol. 29: 999-1007.   DOI
22 Azhar EI, El-Kafrawy SA, Farraj SA, Hassan AM, Al-Saeed MS, Hashem AM, et al. 2014. Evidence for camel-to-human transmission of MERS coronavirus. N. Engl. J. Med. 370: 2499-2505.   DOI
23 van den Brand JM, Smits SL, Haagmans BL. 2015. Pathogenesis of Middle East respiratory syndrome coronavirus. J. Pathol. 235: 175-184.   DOI
24 Widagdo W, Sooksawasdi Na Ayudhya S, Hundie GB, Haagmans BL. 2019. Host Determinants of MERS-CoV Transmission and Pathogenesis. Viruses 11(3). pii: E280.
25 Mubarak A, Alturaiki W, Hemida MG. 2019. Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development. J. Immunol. Res. 2019: 6491738.   DOI
26 Banerjee A, Falzarano D, Rapin N, Lew J, 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(2). pii: E152.
27 Haagmans BL, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M, Myers R, et al. 2014. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect. Dis. 14: 140-145.   DOI
28 Anthony SJ, Gilardi K, Menachery VD, Goldstein T, Ssebide B, Mbabazi R, et al. 2017. Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus. MBio. 8(2). pii: e00373-17.
29 Anthony SJ, Johnson CK, Greig DJ, Kramer S, Che X, Wells H, et al. 2017. Global patterns in coronavirus diversity. Virus Evol. 3: vex012.   DOI
30 Hu J, Lou DH, Carow B, Winerdal ME, Rottenberg M, Wikstrom AC, et al. 2012. LPS regulates SOCS2 transcription in a Type I Interferon dependent autocrine-paracrine loop. PLoS One 7(1): e30166.   DOI
31 Song JW, Guan M, Zhao ZW, Zhang JJ. 2015. Type I interferons function as autocrine and paracrine factors to induce autotaxin in response to TLR activation. PLoS One 10(8): e0136629.   DOI
32 Hasan MT, Jang WJ, Tak JY, Lee BJ, Kim KW, Hur SW, et al. 2018. Effects of Lactococcus lactis subsp. lactis I2 with beta- Glucooligosaccharides on growth, innate immunity and Streptococcosis resistance in olive flounder (Paralichthys olivaceus). J. Microbiol. Biotechnol. 28: 1433-1442.   DOI
33 Ferguson NM, Van Kerkhove MD. 2014. Identification of MERS-CoV in dromedary camels. Lancet Infect. Dis. 14: 93-94.   DOI
34 Goldstein SA, Weiss SR. 2017. Origins and pathogenesis of Middle East respiratory syndrome-associated coronavirus: recent advances. F1000Res. 6: 1628.   DOI
35 Hu B, Zeng LP, Yang XL, Ge XY, Zhang W, Li B, et al. 2017. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog. 13: e1006698.   DOI
36 Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, et al. 2005. Bats are natural reservoirs of SARS-like coronaviruses. Science 310: 676-679.   DOI
37 Yu P, Hu B, Shi ZL, Cui J. 2019. Geographical structure of bat SARS-related coronaviruses. Infect. Genet. Evol. 69: 224-229.   DOI
38 Zhou P, Fan H, Lan T, Yang XL, Shi WF, Zhang W, et al. 2018. Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 556: 255-258.   DOI
39 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.   DOI
40 Liu S, Yu X, Wang Q, Liu Z, Xiao Q, Hou P, et al. 2017. Specific expression of interferon-gamma induced by synergistic activation mediator-derived systems activates innate immunity and inhibits Tumorigenesis. J. Microbiol. Biotechnol. 27: 1855-1866.   DOI
41 Jo G, Jeong MS, Wi J, Kim DH, Kim S, Kim D, et al. 2018. Generation and characterization of a neutralizing human monoclonal antibody to Hepatitis B Virus PreS1 from a Phage-Displayed human synthetic fab library. J. Microbiol. Biotechnol. 28: 1376-1383.   DOI
42 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.   DOI
43 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.   DOI
44 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.   DOI
45 Ngueyen TTN, Kim SJ, Lee JY, Myoung J. 2019. Zika virus proteins NS2A and NS4A are major antagonists that reduce IFN-beta promoter activity induced by the MDA5/RIG-I signaling pathway. J. Microbiol. Biotechnol. 29: 1665-1674.   DOI
46 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.   DOI
47 Huang YW, Dickerman AW, Pineyro P, Li L, Fang L, Kiehne R, et al. 2013. Origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the United States. MBio. 4: e00737-00713.
48 Hayman DT. 2016. Bats as Viral Reservoirs. Annu. Rev. Virol. 3: 77-99.   DOI
49 Takeuchi O, Akira S. 2010. Pattern recognition receptors and inflammation. Cell 140: 805-820.   DOI
50 Luis AD, Hayman DT, O'Shea TJ, Cryan PM, Gilbert AT, Pulliam JR, et al. 2013. A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special? Proc. Biol. Sci. 280: 20122753.
51 Kang S, Myoung J. 2017. Host innate immunity against hepatitis E virus and viral evasion mechanisms. J. Microbiol. Biotechnol. 27: 1727-1735.   DOI
52 Theofilopoulos AN, Baccala R, Beutler B, Kono DH. 2005. Type I interferons (alpha/beta) in immunity and autoimmunity. Annu. Rev. Immunol. 23: 307-336.   DOI
53 Xi Y, Day SL, Jackson RJ, Ranasinghe C. 2012. Role of novel type I interferon epsilon in viral infection and mucosal immunity. Mucosal Immunol. 5: 610-622.   DOI
54 Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. 2015. Type I interferons in anticancer immunity. Nat. Rev. Immunol. 15: 405-414.   DOI
55 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.   DOI
56 Akira S, Uematsu S, Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell 124: 783-801.   DOI
57 Fujita T, Onoguchi K, Onomoto K, Hirai R, Yoneyama M. 2007. Triggering antiviral response by RIG-I-related RNA helicases. Biochimie 89: 754-760.   DOI