1887

Abstract

The type I IFN-mediated immune response is the first line of antiviral defence. Coronaviruses, like many other viruses, have evolved mechanisms to evade this innate response, ensuring their survival. Several coronavirus accessory genes play a central role in these pathways, but for feline coronaviruses this has never to our knowledge been studied. As it has been demonstrated previously that ORF7 is essential for efficient replication and virulence of feline infectious peritonitis virus (FIPV), the role of this ORF in the evasion of the IFN-α antiviral response was investigated. Deletion of ORF7 from FIPV strain 79-1146 (FIPV-Δ7) rendered the virus more susceptible to IFN-α treatment. Given that ORF7 encodes two proteins, 7a and 7b, it was further explored which of these proteins is active in this mechanism. Providing 7a protein rescued the mutant FIPV-Δ7 from IFN sensitivity, which was not achieved by addition of 7b protein. Nevertheless, addition of protein 7a to FIPV-Δ3Δ7, a FIPV mutant deleted in both ORF3 and ORF7, could no longer increase the replication capacity of this mutant in the presence of IFN. These results indicate that FIPV 7a protein is a type I IFN antagonist and protects the virus from the antiviral state induced by IFN, but it needs the presence of ORF3-encoded proteins to exert its antagonistic function.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.058743-0
2014-02-01
2019-09-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/2/393.html?itemId=/content/journal/jgv/10.1099/vir.0.058743-0&mimeType=html&fmt=ahah

References

  1. Addie D. D. , Toth S. , Murray G. D. , Jarrett O. . ( 1995; ). Risk of feline infectious peritonitis in cats naturally infected with feline coronavirus. . Am J Vet Res 56:, 429–434.[PubMed]
    [Google Scholar]
  2. Belkowski L. S. , Sen G. C. . ( 1987; ). Inhibition of vesicular stomatitis viral mRNA synthesis by interferons. . J Virol 61:, 653–660.[PubMed]
    [Google Scholar]
  3. Chang H. W. , de Groot R. J. , Egberink H. F. , Rottier P. J. . ( 2010; ). Feline infectious peritonitis: insights into feline coronavirus pathobiogenesis and epidemiology based on genetic analysis of the viral 3c gene. . J Gen Virol 91:, 415–420. [CrossRef] [PubMed]
    [Google Scholar]
  4. Cornelissen E. , Dewerchin H. L. , Van Hamme E. , Nauwynck H. J. . ( 2007; ). Absence of surface expression of feline infectious peritonitis virus (FIPV) antigens on infected cells isolated from cats with FIP. . Vet Microbiol 121:, 131–137. [CrossRef] [PubMed]
    [Google Scholar]
  5. Cornelissen E. , Dewerchin H. L. , Van Hamme E. , Nauwynck H. J. . ( 2009; ). Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells. . Virus Res 144:, 285–289. [CrossRef] [PubMed]
    [Google Scholar]
  6. Cruz J. L. , Sola I. , Becares M. , Alberca B. , Plana J. , Enjuanes L. , Zuñiga S. . ( 2011; ). Coronavirus gene 7 counteracts host defenses and modulates virus virulence. . PLoS Pathog 7:, e1002090. [CrossRef] [PubMed]
    [Google Scholar]
  7. Dedeurwaerder A. , Desmarets L. M. , Olyslaegers D. A. , Vermeulen B. L. , Dewerchin H. L. , Nauwynck H. J. . ( 2013; ). The role of accessory proteins in the replication of feline infectious peritonitis virus in peripheral blood monocytes. . Vet Microbiol 162:, 447–455. [CrossRef] [PubMed]
    [Google Scholar]
  8. Desmarets L. M. , Theuns S. , Olyslaegers D. A. , Dedeurwaerder A. , Vermeulen B. L. , Roukaerts I. D. , Nauwynck H. J. . ( 2013; ). Establishment of feline intestinal epithelial cell cultures for the propagation and study of feline enteric coronaviruses. . Vet Res 44:, 71. [CrossRef] [PubMed]
    [Google Scholar]
  9. Dewerchin H. L. , Cornelissen E. , Nauwynck H. J. . ( 2005; ). Replication of feline coronaviruses in peripheral blood monocytes. . Arch Virol 150:, 2483–2500. [CrossRef] [PubMed]
    [Google Scholar]
  10. Dewerchin H. L. , Cornelissen E. , Van Hamme E. , Smits K. , Verhasselt B. , Nauwynck H. J. . ( 2008; ). Surface-expressed viral proteins in feline infectious peritonitis virus-infected monocytes are internalized through a clathrin- and caveolae-independent pathway. . J Gen Virol 89:, 2731–2740. [CrossRef] [PubMed]
    [Google Scholar]
  11. Drosten C. , Günther S. , Preiser W. , van der Werf S. , Brodt H. R. , Becker S. , Rabenau H. , Panning M. , Kolesnikova L. . & other authors ( 2003; ). Identification of a novel coronavirus in patients with severe acute respiratory syndrome. . N Engl J Med 348:, 1967–1976. [CrossRef] [PubMed]
    [Google Scholar]
  12. Enjuanes L. , Almazán F. , Sola I. , Zuñiga S. . ( 2006; ). Biochemical aspects of coronavirus replication and virus–host interaction. . Annu Rev Microbiol 60:, 211–230. [CrossRef] [PubMed]
    [Google Scholar]
  13. Gale M. Jr , Sen G. C. . ( 2009; ). Viral evasion of the interferon system. . J Interferon Cytokine Res 29:, 475–476. [CrossRef] [PubMed]
    [Google Scholar]
  14. Gorbalenya A. E. , Enjuanes L. , Ziebuhr J. , Snijder E. J. . ( 2006; ). Nidovirales: evolving the largest RNA virus genome. . Virus Res 117:, 17–37. [CrossRef] [PubMed]
    [Google Scholar]
  15. Grandvaux N. , tenOever B. R. , Servant M. J. , Hiscott J. . ( 2002; ). The interferon antiviral response: from viral invasion to evasion. . Curr Opin Infect Dis 15:, 259–267. [CrossRef] [PubMed]
    [Google Scholar]
  16. Haijema B. J. , Volders H. , Rottier P. J. . ( 2004; ). Live, attenuated coronavirus vaccines through the directed deletion of group-specific genes provide protection against feline infectious peritonitis. . J Virol 78:, 3863–3871. [CrossRef] [PubMed]
    [Google Scholar]
  17. Hayashi T. , Watabe Y. , Nakayama H. , Fujiwara K. . ( 1982; ). Enteritis due to feline infectious peritonitis virus. . Nippon Juigaku Zasshi 44:, 97–106. [CrossRef] [PubMed]
    [Google Scholar]
  18. Herrewegh A. A. , Vennema H. , Horzinek M. C. , Rottier P. J. , de Groot R. J. . ( 1995; ). The molecular genetics of feline coronaviruses: comparative sequence analysis of the ORF7a/7b transcription unit of different biotypes. . Virology 212:, 622–631. [CrossRef] [PubMed]
    [Google Scholar]
  19. Herrewegh A. A. , Mähler M. , Hedrich H. J. , Haagmans B. L. , Egberink H. F. , Horzinek M. C. , Rottier P. J. , de Groot R. J. . ( 1997; ). Persistence and evolution of feline coronavirus in a closed cat-breeding colony. . Virology 234:, 349–363. [CrossRef] [PubMed]
    [Google Scholar]
  20. Kamitani W. , Narayanan K. , Huang C. , Lokugamage K. , Ikegami T. , Ito N. , Kubo H. , Makino S. . ( 2006; ). Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. . Proc Natl Acad Sci U S A 103:, 12885–12890. [CrossRef] [PubMed]
    [Google Scholar]
  21. Kennedy M. , Boedeker N. , Gibbs P. , Kania S. . ( 2001; ). Deletions in the 7a ORF of feline coronavirus associated with an epidemic of feline infectious peritonitis. . Vet Microbiol 81:, 227–234. [CrossRef] [PubMed]
    [Google Scholar]
  22. Kennedy M. A. , Abd-Eldaim M. , Zika S. E. , Mankin J. M. , Kania S. A. . ( 2008; ). Evaluation of antibodies against feline coronavirus 7b protein for diagnosis of feline infectious peritonitis in cats. . Am J Vet Res 69:, 1179–1182. [CrossRef] [PubMed]
    [Google Scholar]
  23. Kipar A. , Meli M. L. , Baptiste K. E. , Bowker L. J. , Lutz H. . ( 2010; ). Sites of feline coronavirus persistence in healthy cats. . J Gen Virol 91:, 1698–1707. [CrossRef] [PubMed]
    [Google Scholar]
  24. Koetzner C. A. , Kuo L. , Goebel S. J. , Dean A. B. , Parker M. M. , Masters P. S. . ( 2010; ). Accessory protein 5a is a major antagonist of the antiviral action of interferon against murine coronavirus. . J Virol 84:, 8262–8274. [CrossRef] [PubMed]
    [Google Scholar]
  25. Kopecky-Bromberg S. A. , Martinez-Sobrido L. , Palese P. . ( 2006; ). 7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase. . J Virol 80:, 785–793. [CrossRef] [PubMed]
    [Google Scholar]
  26. Kopecky-Bromberg S. A. , Martínez-Sobrido L. , Frieman M. , Baric R. A. , Palese P. . ( 2007; ). Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. . J Virol 81:, 548–557. [CrossRef] [PubMed]
    [Google Scholar]
  27. Licitra B. N. , Millet J. K. , Regan A. D. , Hamilton B. S. , Rinaldi V. D. , Duhamel G. E. , Whittaker G. R. . ( 2013; ). Mutation in spike protein cleavage site and pathogenesis of feline coronavirus. . Emerg Infect Dis 19:, 1066–1073. [CrossRef] [PubMed]
    [Google Scholar]
  28. Lin C. N. , Su B. L. , Huang H. P. , Lee J. J. , Hsieh M. W. , Chueh L. L. . ( 2009; ). Field strain feline coronaviruses with small deletions in ORF7b associated with both enteric infection and feline infectious peritonitis. . J Feline Med Surg 11:, 413–419. [CrossRef] [PubMed]
    [Google Scholar]
  29. Medzhitov R. , Janeway C. A. Jr . ( 1997; ). Innate immunity: the virtues of a nonclonal system of recognition. . Cell 91:, 295–298. [CrossRef] [PubMed]
    [Google Scholar]
  30. Meli M. , Kipar A. , Müller C. , Jenal K. , Gönczi E. , Borel N. , Gunn-Moore D. , Chalmers S. , Lin F. . & other authors ( 2004; ). High viral loads despite absence of clinical and pathological findings in cats experimentally infected with feline coronavirus (FCoV) type I and in naturally FCoV-infected cats. . J Feline Med Surg 6:, 69–81. [CrossRef] [PubMed]
    [Google Scholar]
  31. Mochizuki M. , Nakatani H. , Yoshida M. . ( 1994; ). Inhibitory effects of recombinant feline interferon on the replication of feline enteropathogenic viruses in vitro. . Vet Microbiol 39:, 145–152. [CrossRef] [PubMed]
    [Google Scholar]
  32. Myrrha L. W. , Silva F. M. , Peternelli E. F. , Junior A. S. , Resende M. , de Almeida M. R. . ( 2011; ). The paradox of feline coronavirus pathogenesis: a review. . Adv Virol 2011:, 109849.[PubMed] [CrossRef]
    [Google Scholar]
  33. Pedersen N. C. , Boyle J. F. , Floyd K. , Fudge A. , Barker J. . ( 1981; ). An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis. . Am J Vet Res 42:, 368–377.[PubMed]
    [Google Scholar]
  34. Pedersen N. C. , Liu H. , Scarlett J. , Leutenegger C. M. , Golovko L. , Kennedy H. , Kamal F. M. . ( 2012; ). Feline infectious peritonitis: role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats. . Virus Res 165:, 17–28. [CrossRef] [PubMed]
    [Google Scholar]
  35. Randall R. E. , Goodbourn S. . ( 2008; ). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. . J Gen Virol 89:, 1–47. [CrossRef] [PubMed]
    [Google Scholar]
  36. Reed L. J. , Muench H. . ( 1938; ). A simple method of estimating fifty per cent endpoints. . Am J Hyg 27:, 493–497.
    [Google Scholar]
  37. Repetto G. , del Peso A. , Zurita J. L. . ( 2008; ). Neutral red uptake assay for the estimation of cell viability/cytotoxicity. . Nat Protoc 3:, 1125–1131. [CrossRef] [PubMed]
    [Google Scholar]
  38. Rottier P. J. , Nakamura K. , Schellen P. , Volders H. , Haijema B. J. . ( 2005; ). Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein. . J Virol 79:, 14122–14130. [CrossRef] [PubMed]
    [Google Scholar]
  39. Spaan W. , Cavanagh D. , Horzinek M. C. . ( 1988; ). Coronaviruses: structure and genome expression. . J Gen Virol 69:, 2939–2952. [CrossRef] [PubMed]
    [Google Scholar]
  40. Stoddart C. A. , Scott F. W. . ( 1989; ). Intrinsic resistance of feline peritoneal macrophages to coronavirus infection correlates with in vivo virulence. . J Virol 63:, 436–440.[PubMed]
    [Google Scholar]
  41. Takeuchi O. , Akira S. . ( 2009; ). Innate immunity to virus infection. . Immunol Rev 227:, 75–86. [CrossRef] [PubMed]
    [Google Scholar]
  42. Taylor K. E. , Mossman K. L. . ( 2013; ). Recent advances in understanding viral evasion of type I interferon. . Immunology 138:, 190–197. [CrossRef] [PubMed]
    [Google Scholar]
  43. Thiel V. . ( 2007; ). Coronaviruses: Molecular and Cellular Biology. Wymondham, Norfolk:: Caister Academic Press;.
    [Google Scholar]
  44. Thompson S. R. , Sarnow P. . ( 2000; ). Regulation of host cell translation by viruses and effects on cell function. . Curr Opin Microbiol 3:, 366–370. [CrossRef] [PubMed]
    [Google Scholar]
  45. Vennema H. , Heijnen L. , Rottier P. J. , Horzinek M. C. , Spaan W. J. . ( 1992; ). A novel glycoprotein of feline infectious peritonitis coronavirus contains a KDEL-like endoplasmic reticulum retention signal. . J Virol 66:, 4951–4956.[PubMed]
    [Google Scholar]
  46. Vennema H. , Poland A. , Foley J. , Pedersen N. C. . ( 1998; ). Feline infectious peritonitis viruses arise by mutation from endemic feline enteric coronaviruses. . Virology 243:, 150–157. [CrossRef] [PubMed]
    [Google Scholar]
  47. Vermeulen B. L. . ( 2013; ). The role of cell-mediated immunity during coronavirus infections in cats: opportunities for therapeutic avenues? PhD thesis, Ghent University;, Belgium:.
    [Google Scholar]
  48. Vermeulen B. L. , Devriendt B. , Olyslaegers D. A. , Dedeurwaerder A. , Desmarets L. M. , Favoreel H. W. , Dewerchin H. L. , Nauwynck H. J. . ( 2013; ). Suppression of NK cells and regulatory T lymphocytes in cats naturally infected with feline infectious peritonitis virus. . Vet Microbiol 164:, 46–59. [CrossRef] [PubMed]
    [Google Scholar]
  49. Wang X. , Liao Y. , Yap P. L. , Png K. J. , Tam J. P. , Liu D. X. . ( 2009; ). Inhibition of protein kinase R activation and upregulation of GADD34 expression play a synergistic role in facilitating coronavirus replication by maintaining de novo protein synthesis in virus-infected cells. . J Virol 83:, 12462–12472. [CrossRef] [PubMed]
    [Google Scholar]
  50. Ward J. M. , Munn R. J. , Gribble D. H. , Dungworth D. L. . ( 1968; ). An observation of feline infectious peritonitis. . Vet Rec 83:, 416–417. [CrossRef] [PubMed]
    [Google Scholar]
  51. Weiss R. C. , Cox N. R. , Oostrom-Ram T. . ( 1990; ). Effect of interferon or Propionibacterium acnes on the course of experimentally induced feline infectious peritonitis in specific-pathogen-free and random-source cats. . Am J Vet Res 51:, 726–733.[PubMed]
    [Google Scholar]
  52. Ye Y. , Hauns K. , Langland J. O. , Jacobs B. L. , Hogue B. G. . ( 2007; ). Mouse hepatitis coronavirus A59 nucleocapsid protein is a type I interferon antagonist. . J Virol 81:, 2554–2563. [CrossRef] [PubMed]
    [Google Scholar]
  53. Zaki A. M. , van Boheemen S. , Bestebroer T. M. , Osterhaus A. D. , Fouchier R. A. . ( 2012; ). Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. . N Engl J Med 367:, 1814–1820. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.058743-0
Loading
/content/journal/jgv/10.1099/vir.0.058743-0
Loading

Data & Media loading...

Most Cited This Month

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