Abstract
Avian infectious bronchitis virus (IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3-5 days post inoculation (dpi) and in the kidney at 8 dpi, with heavy viral loads at 1-11 and 1-28 dpi, respectively. The expression of mRNAs encoding Toll-like receptor (TLR) 3 and TLR7 were upregulated at 3-8 dpi, and that of TIR-domain-containing adapter-inducing interferon (IFN) β (TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88 (MyD88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor (TRAF) 3 and TRAF6 were upregulated expression in both tissues. Moreover, melanoma differentiation-associated protein 5 (MDA5), laboratory of genetics and physiology 2 (LGP2), stimulator of IFN genes (STING), and mitochondrial antiviral signaling protein (MAVS), as well as TANK binding kinase 1 (TBK1), inhibitor of kappaB kinase (IKK) ε, IKKα, IKKβ, IFN regulatory factor (IRF) 7, nuclear factor of kappaB (NF-ĸB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β (MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally, consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.
References
Awad F, Chhabra R, Baylis M, Ganapathy K. 2014. An overview of infectious bronchitis virus in chickens. World Poultry Sci J, 70: 375–383.
Benyeda Z, Mato T, Suveges T, Szabo E, Kardi V, Abonyi-Toth Z, Rusvai M, Palya V. 2009. Comparison of the pathogenicity of QX-like, M41 and 793/B infectious bronchitis strains from different pathological conditions. Avian Pathol, 38: 449–456.
Cao L, Ge X, Gao Y, Ren Y, Ren X, Li G. 2015. Porcine epidemic diarrhea virus infection induces NF-kappaB activation through the TLR2, TLR3 and TLR9 pathways in porcine intestinal epithelial cells. J Gen Virol, 96: 1757–1767.
Cavanagh D. 2005. Coronaviruses in poultry and other birds. Avian Pathol, 34: 439–448.
Cavanagh D. 2007. Coronavirus avian infectious bronchitis virus. Vet Res, 38: 281–297.
Chen L, Zhang T, Han Z, Liang S, Xu Y, Xu Q, Chen Y, Zhao Y, Shao Y, Li H, Wang K, Kong X, Liu S. 2015. Molecular and antigenic characteristics of Massachusetts genotype infectious bronchitis coronavirus in China. Vet Microbiol. 181: 241–251.
Cheng Y, Sun Y, Wang H, Yan Y, Ding C, Sun J. 2015. Chicken STING Mediates Activation of the IFN Gene Independently of the RIG-I Gene. J Immunol, 195: 3922–3936.
Chousalkar KK, Roberts JR, Reece R. 2007. Comparative histopathology of two serotypes of infectious bronchitis virus (T and n1/88) in laying hens and cockerels. Poult Sci, 86: 50–58.
Cong F, Liu X, Han Z, Shao Y, Kong X, Liu S. 2013. Transcriptome analysis of chicken kidney tissues following coronavirus avian infectious bronchitis virus infection. BMC Genomics, 14: 743.
Cook JK, Jackwood M, Jones RC. 2012. The long view: 40 years of infectious bronchitis research. Avian Pathol, 41: 239–250.
Dar A, Tikoo S, Potter A, Babiuk LA, Townsend H, Gerdts V, Mutwiri G. 2014. CpG-ODNs induced changes in cytokine/chemokines genes expression associated with suppression of infectious bronchitis virus replication in chicken lungs. Vet Immunol Immunopathol, 160: 209–217.
Dosch SF, Mahajan SD, Collins AR. 2009. SARS coronavirus spike protein-induced innate immune response occurs via activation of the NF-kappaB pathway in human monocyte macrophages in vitro. Virus Res, 142: 19–27.
Fan WQ, Wang HN, Zhang Y, Guan ZB, Wang T, Xu CW, Zhang AY, Yang X. 2012. Comparative dynamic distribution of avian infectious bronchitis virus M41, H120, and SAIBK strains by quantitative real-time RT-PCR in SPF chickens. Biosci Biotechnol Biochem, 76: 2255–2260.
Frieman M, Ratia K, Johnston RE, Mesecar AD, Baric RS. 2009. Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling. J Virol, 83: 6689–6705.
Guo X, Rosa AJ, Chen DG, Wang X. 2008. Molecular mechanisms of primary and secondary mucosal immunity using avian infectious bronchitis virus as a model system. Vet Immunol Immunopathol, 121: 332–343.
Ignjatovic J, Ashton DF, Reece R, Scott P, Hooper P. 2002. Pathogenicity of Australian strains of avian infectious bronchitis virus. J Comp Pathol, 126: 115–123.
Jang H, Koo BS, Jeon EO, Lee HR, Lee SM, Mo IP. 2013. Altered pro-inflammatory cytokine mRNA levels in chickens infected with infectious bronchitis virus. Poult Sci, 92: 2290–2298.
Kameka AM, Haddadi S, Kim DS, Cork SC, Abdul-Careem MF. 2014. Induction of innate immune response following infectious bronchitis corona virus infection in the respiratory tract of chickens. Virology, 450–451: 114–121.
Karpala AJ, Lowenthal JW, Bean AG. 2008. Activation of the TLR3 pathway regulates IFNbeta production in chickens. Dev Comp Immunol, 32: 435–444.
Kawasaki T, Kawai T. 2014. Toll-Like Receptor Signaling Pathways. Front Immunol, 5: 46.
Kint J, Fernandez-Gutierrez M, Maier HJ, Britton P, Langereis MA, Koumans J, Wiegertjes GF, Forlenza M. 2015. Activation of the Chicken Type I Interferon Response by Infectious Bronchitis Coronavirus. J Virol, 89: 1156–1167.
Law HK, Cheung CY, Sia SF, Chan YO, Peiris JS, Lau YL. 2009. Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells. BMC Immunol, 10: 35.
Li M, Jiang JJ, He K, Sun XK, Liang XB, Zhang YQ, Liang YD, Mo ML, Wei TC, W P. 2012. The detection and comparative analysis of antibodies IB in clinical serum samples using the self-developed Indirect N-ELISA kits. Guangxi J Animal Husb Vet Med, 28: 195–197. (In Chinese)
Li M, Wang XY, Wei P, Chen QY, Wei ZJ, Mo ML. 2012. Serotype and genotype diversity of infectious bronchitis viruses isolated during 1985-2008 in Guangxi, China. Arch Virol, 157: 467–474.
Liniger M, Summerfield A, Zimmer G, McCullough KC, Ruggli N. 2011. Chicken Cells Sense Influenza A Virus Infection through MDA5 and CARDIF Signaling Involving LGP2. J Virol, 86: 705–717.
Li J, Liu Y, Zhang X. 2010. Murine Coronavirus Induces Type I Interferon in Oligodendrocytes through Recognition by RIG-I and MDA5. J Virol, 84: 6472–6482.
Li Y, Bang D, Handberg K, Jorgensen P, Zhang M. 2005. Evaluation of the suitability of six host genes as internal control in real-time RT-PCR assays in chicken embryo cell cultures infected with infectious bursal disease virus. Vet Microbiol, 110: 155–165.
Mazaleuskaya L, Veltrop R, Ikpeze N, Martin-Garcia J, Navas-Martin S. 2012. Protective role of Toll-like Receptor 3-induced type I interferon in murine coronavirus infection of macrophages. Viruses, 4: 901–923.
Mo ML, Cheng QY, Hou JL, Fan WS, Li M, Wei P, Wei TC, Wei ZJ. 2011. Development of a real-time PCR assay for detection of infectious bronchitis virus. China Poultry, 41: 193–198. (In Chinese)
Mo ML, Li M, Huang BC, Fan WS, Wei P, Wei TC, Cheng QY, Wei ZJ, Lang YH. 2013. Molecular characterization of major structural protein genes of avian coronavirus infectious bronchitis virus isolates in southern china. Viruses, 5: 3007–3020.
Mogensen TH. 2009. Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses. Clin Microbiol Rev, 22: 240.
Nakhaei P, Genin P, Civas A, Hiscott J. 2009. RIG-I-like receptors: sensing and responding to RNA virus infection. Semin Immunol, 21:215–222.
Nii T, Isobe N, Yoshimura Y. 2014. Effects of avian infectious bronchitis virus antigen on eggshell formation and immunoreaction in hen oviduct. Theriogenology, 81: 1129–1138.
Okino CH, Santos IL, Fernando FS, Alessi AC, Wang X, Montassier HJ. 2014. Inflammatory and cell-mediated immune responses in the respiratory tract of chickens to infection with avian infectious bronchitis virus. Viral Immunol, 27: 383–391.
Panda S, Nilsson JA, Gekara NO. 2015. Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes. Immunity, 43: 647–659.
Pfaffl MW, Horgan GW, Dempfle L. 2002. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res, 30: e36.
Schalk AF, Hawn MC. 1931. An apparently new respiratory disease of baby chicks. J Am Vet Med Assoc, 78: 413–422.
Sheahan T, Morrison TE, Funkhouser W, Uematsu S, Akira S, Baric RS, Heise MT. 2008. MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV. PLoS Pathog, 4: e1000240.
Shi CS, Qi HY, Boularan C, Huang NN, Abu-Asab M, Shelhamer JH, Kehrl JH. 2014. SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J Immunol, 193: 3080–3089.
Smith J, Sadeyen J, Cavanagh D, Kaiser P, Burt DW. 2015. The early immune response to infection of chickens with Infectious Bronchitis Virus (IBV) in susceptible and resistant birds. BMC Vet Res, 11: 256.
Sun L, Xing Y, Chen X, Zheng Y, Yang Y, Nichols DB, Clementz MA, Banach BS, Li K, Baker SC, Chen Z. 2012. Coronavirus papain-like proteases negatively regulate antiviral innate immune response through disruption of STING-mediated signaling. PLoS One, 7: e30802.
Sun Y, Han M, Kim C, Calvert JG, Yoo D. 2012. Interplay between interferon-mediated innate immunity and porcine reproductive and respiratory syndrome virus. Viruses, 4: 424–446.
Takeuchi O, Akira S. 2009. Innate immunity to virus infection. Immunol Rev, 227: 75–86.
Totura AL, Whitmore A, Agnihothram S, Schafer A, Katze MG, Heise MT, Baric RS. 2015. Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection. MBio, 6: e615–e638.
Wickramasinghe INA, de Vries RP, Grone A, de Haan CAM, Verheije MH. 2011. Binding of Avian Coronavirus Spike Proteins to Host Factors Reflects Virus Tropism and Pathogenicity. J Virol, 85: 8903–8912.
Wu B, Peisley A, Richards C, Yao H, Zeng X, Lin C, Chu F, Walz T, Hur S. 2013. Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell, 152: 276–289.
Xu Y, Zhang T, Xu Q, Han Z, Liang S, Shao Y, Ma D, Liu S. 2015. Differential modulation of avian β-defensin and Toll-like receptor expression in chickens infected with infectious bronchitis virus. Appl Microbiol Biot, 99: 9011–9024.
Yu L, Jiang Y, Low S, Wang Z, Nam SJ, Liu W, Kwangac J. 2001. Characterization of three infectious bronchitis virus isolates from China associated with proventriculus in vaccinated chickens. Avian Dis, 45: 416–424.
Zhong Y, Tan YW, Liu DX. 2012. Recent progress in studies of arterivirus- and coronavirus-host interactions. Viruses, 4: 980–1010.
Zou J, Chang M, Nie P, Secombes CJ. 2009. Origin and evolution of the RIG-I like RNA helicase gene family. BMC Evol Biol, 9: 85.
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ORCID: 0000-0003-3903-0509
ORCID: 0000-0003-1159-5145
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He, Y., Xie, Z., Dai, J. et al. Responses of the Toll-like receptor and melanoma differentiation-associated protein 5 signaling pathways to avian infectious bronchitis virus infection in chicks. Virol. Sin. 31, 57–68 (2016). https://doi.org/10.1007/s12250-015-3696-y
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DOI: https://doi.org/10.1007/s12250-015-3696-y
Keywords
- infectious bronchitis virus
- Toll-like receptor signal pathway
- melanoma differentiation-associated protein 5 signal pathway
- cytokines