1887

Abstract

Avian coronavirus infectious bronchitis virus (IBV) infects domestic fowl, resulting in respiratory disease and causing serious losses in unprotected birds. Its control is mainly achieved by using live attenuated vaccines. Here we explored the possibilities for rationally attenuating IBV to improve our knowledge regarding the function of IBV accessory proteins and for the development of next-generation vaccines with the recently established reverse genetic system for IBV H52 based on targeted RNA recombination and selection of recombinant viruses in embryonated eggs. To this aim, we selectively removed accessory genes 3a, 3b, 5a and 5b individually, and rescued the resulting recombinant (r) rIBV-Δ3a, rIBV-Δ3b, rIBV-Δ5a and rIBV-Δ5b. In vitro inoculation of chicken embryo kidney cells with recombinant and wild-type viruses demonstrated that the accessory protein 5b is involved in the delayed activation of the interferon response of the host after IBV infection. Embryo mortality after the inoculation of 8-day-old embryonated chicken eggs with recombinant and wild-type viruses showed that rIBV-Δ3b, rIBV-Δ5a and rIBV-Δ5b had an attenuated phenotype in ovo, with reduced titres at 6 h p.i. and 12 h p.i. for all viruses, while growing to the same titre as wild-type rIBV at 48 h p.i. When administered to 1-day-old chickens, rIBV-Δ3a, rIBV-Δ3b, rIBV-Δ5a and rIBV-Δ5b showed reduced ciliostasis in comparison to the wild-type viruses. In conclusion, individual deletion of accessory genes in IBV H52 resulted in mutant viruses with an attenuated phenotype.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001130
2018-08-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/99/10/1381.html?itemId=/content/journal/jgv/10.1099/jgv.0.001130&mimeType=html&fmt=ahah

References

  1. Jackwood M, de Wit JJ. Infectious bronchitis. In Diseases of Poultry, 13th ed. 2013 pp. 139–159
    [Google Scholar]
  2. Cavanagh D, Casais R, Armesto M, Hodgson T, Izadkhasti S et al. Manipulation of the infectious bronchitis coronavirus genome for vaccine development and analysis of the accessory proteins. Vaccine 2007; 25:5558–5562 [View Article][PubMed]
    [Google Scholar]
  3. Liu DX, Fung TS, Chong KK, Shukla A, Hilgenfeld R. Accessory proteins of SARS-CoV and other coronaviruses. Antiviral Res 2014; 109:97–109 [View Article][PubMed]
    [Google Scholar]
  4. Casais R, Davies M, Cavanagh D, Britton P. Gene 5 of the avian coronavirus infectious bronchitis virus is not essential for replication. J Virol 2005; 79:8065–8078 [View Article][PubMed]
    [Google Scholar]
  5. de Haan CA, Masters PS, Shen X, Weiss S, Rottier PJ. The group-specific murine coronavirus genes are not essential, but their deletion, by reverse genetics, is attenuating in the natural host. Virology 2002; 296:177–189 [View Article][PubMed]
    [Google Scholar]
  6. Haijema BJ, Volders H, Rottier PJ. Live, attenuated coronavirus vaccines through the directed deletion of group-specific genes provide protection against feline infectious peritonitis. J Virol 2004; 78:3863–3871 [View Article][PubMed]
    [Google Scholar]
  7. Hodgson T, Britton P, Cavanagh D. Neither the RNA nor the proteins of open reading frames 3a and 3b of the coronavirus infectious bronchitis virus are essential for replication. J Virol 2006; 80:296–305 [View Article][PubMed]
    [Google Scholar]
  8. Shen S, Wen ZL, Liu DX. Emergence of a coronavirus infectious bronchitis virus mutant with a truncated 3b gene: functional characterization of the 3b protein in pathogenesis and replication. Virology 2003; 311:16–27 [View Article][PubMed]
    [Google Scholar]
  9. Casais R, Thiel V, Siddell SG, Cavanagh D, Britton P. Reverse genetics system for the avian coronavirus infectious bronchitis virus. J Virol 2001; 75:12359–12369 [View Article][PubMed]
    [Google Scholar]
  10. van Beurden SJ, Berends AJ, Krämer-Kühl A, Spekreijse D, Chénard G et al. A reverse genetics system for avian coronavirus infectious bronchitis virus based on targeted RNA recombination. Virol J 2017; 14:109 [View Article][PubMed]
    [Google Scholar]
  11. van Beurden SJ, Berends AJ, Krämer-Kühl A, Spekreijse D, Chenard G et al. Recombinant live attenuated avian coronavirus vaccines with deletions in the accessory genes 3ab and/or 5ab protect against infectious bronchitis in chickens. Vaccine 2018; 36:1085–1092 [View Article][PubMed]
    [Google Scholar]
  12. Youn S, Leibowitz JL, Collisson EW. In vitro assembled, recombinant infectious bronchitis viruses demonstrate that the 5a open reading frame is not essential for replication. Virology 2005; 332:206–215 [View Article][PubMed]
    [Google Scholar]
  13. Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev 2001; 14:778–809 [View Article][PubMed]
    [Google Scholar]
  14. Dedeurwaerder A, Olyslaegers DA, Desmarets LM, Roukaerts ID, Theuns S et al. ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response. J Gen Virol 2014; 95:393–402 [View Article][PubMed]
    [Google Scholar]
  15. Koetzner CA, Kuo L, Goebel SJ, Dean AB, Parker MM et al. Accessory protein 5a is a major antagonist of the antiviral action of interferon against murine coronavirus. J Virol 2010; 84:8262–8274 [View Article][PubMed]
    [Google Scholar]
  16. Abdul-Careem MF, Hunter DB, Lambourne MD, Barta J, Sharif S. Ontogeny of cytokine gene expression in the chicken spleen. Poult Sci 2007; 86:1351–1355 [View Article][PubMed]
    [Google Scholar]
  17. Leitão JM, Esteves da Silva JC. Firefly luciferase inhibition. J Photochem Photobiol B 2010; 101:1–8 [View Article][PubMed]
    [Google Scholar]
  18. Thorne N, Shen M, Lea WA, Simeonov A, Lovell S et al. Firefly luciferase in chemical biology: a compendium of inhibitors, mechanistic evaluation of chemotypes, and suggested use as a reporter. Chem Biol 2012; 19:1060–1072 [View Article][PubMed]
    [Google Scholar]
  19. Kint J, Langereis MA, Maier HJ, Britton P, van Kuppeveld FJ et al. Infectious bronchitis coronavirus limits interferon production by inducing a host shutoff that requires accessory protein 5b. J Virol 2016; 90:7519–7528 [View Article][PubMed]
    [Google Scholar]
  20. Kint J, Dickhout A, Kutter J, Maier HJ, Britton P et al. Infectious bronchitis coronavirus inhibits STAT1 signaling and requires accessory proteins for resistance to type I interferon activity. J Virol 2015; 89:12047–12057 [View Article][PubMed]
    [Google Scholar]
  21. Kint J, Fernandez-Gutierrez M, Maier HJ, Britton P, Langereis MA et al. Activation of the chicken type I interferon response by infectious bronchitis coronavirus. J Virol 2015; 89:1156–1167 [View Article][PubMed]
    [Google Scholar]
  22. Zhao J, Falcón A, Zhou H, Netland J, Enjuanes L et al. Severe acute respiratory syndrome coronavirus protein 6 is required for optimal replication. J Virol 2009; 83:2368–2373 [View Article][PubMed]
    [Google Scholar]
  23. Kuo L, Godeke GJ, Raamsman MJ, Masters PS, Rottier PJ. Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: crossing the host cell species barrier. J Virol 2000; 74:1393–1406 [View Article][PubMed]
    [Google Scholar]
  24. Schwarz H, Harlin O, Ohnemus A, Kaspers B, Staeheli P. Synthesis of IFN-beta by virus-infected chicken embryo cells demonstrated with specific antisera and a new bioassay. J Interferon Cytokine Res 2004; 24:179–184 [View Article][PubMed]
    [Google Scholar]
  25. Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. American Journal of Hygiene 1938; 493:493–497
    [Google Scholar]
  26. Cavanagh D, Elus MM, Cook JK. Relationship between sequence variation in the S1 spike protein of infectious bronchitis virus and the extent of cross-protection in vivo. Avian Pathol 1997; 26:63–74 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001130
Loading
/content/journal/jgv/10.1099/jgv.0.001130
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error