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ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response

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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 in vitro and virulence in vivo of feline infectious peritonitis virus (FIPV), the role of this ORF in the evasion of the IFN-alpha antiviral response was investigated. Deletion of ORF7 from FIPV strain 79-1146 (FIPV-Delta 7) rendered the virus more susceptible to IFN-a 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 in trans rescued the mutant FIPV-Delta 7 from IFN sensitivity, which was not achieved by addition of 7b protein. Nevertheless, addition of protein 7a to FIPV-Delta 3 Delta 7, 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.
Keywords
EXPRESSION, CATS, I INTERFERON, 3C GENE, SPIKE PROTEIN, ENTERIC CORONAVIRUSES, INNATE IMMUNITY, CORONAVIRUS REPLICATION, ACUTE RESPIRATORY SYNDROME, PERIPHERAL-BLOOD MONOCYTES

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Citation

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MLA
Dedeurwaerder, Annelike, Dominique Olyslaegers, Lowiese Desmarets, et al. “ORF7-encoded Accessory Protein 7a of Feline Infectious Peritonitis Virus as a Counteragent Against IFN-α-induced Antiviral Response.” JOURNAL OF GENERAL VIROLOGY 95 (2014): 393–402. Print.
APA
Dedeurwaerder, A., Olyslaegers, D., Desmarets, L., Roukaerts, I., Theuns, S., & Nauwynck, H. (2014). ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response. JOURNAL OF GENERAL VIROLOGY, 95, 393–402.
Chicago author-date
Dedeurwaerder, Annelike, Dominique Olyslaegers, Lowiese Desmarets, Inge Roukaerts, Sebastiaan Theuns, and Hans Nauwynck. 2014. “ORF7-encoded Accessory Protein 7a of Feline Infectious Peritonitis Virus as a Counteragent Against IFN-α-induced Antiviral Response.” Journal of General Virology 95: 393–402.
Chicago author-date (all authors)
Dedeurwaerder, Annelike, Dominique Olyslaegers, Lowiese Desmarets, Inge Roukaerts, Sebastiaan Theuns, and Hans Nauwynck. 2014. “ORF7-encoded Accessory Protein 7a of Feline Infectious Peritonitis Virus as a Counteragent Against IFN-α-induced Antiviral Response.” Journal of General Virology 95: 393–402.
Vancouver
1.
Dedeurwaerder A, Olyslaegers D, Desmarets L, Roukaerts I, Theuns S, Nauwynck H. ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response. JOURNAL OF GENERAL VIROLOGY. 2014;95:393–402.
IEEE
[1]
A. Dedeurwaerder, D. Olyslaegers, L. Desmarets, I. Roukaerts, S. Theuns, and H. Nauwynck, “ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response,” JOURNAL OF GENERAL VIROLOGY, vol. 95, pp. 393–402, 2014.
@article{5661726,
  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 in vitro and virulence in vivo of feline infectious peritonitis virus (FIPV), the role of this ORF in the evasion of the IFN-alpha antiviral response was investigated. Deletion of ORF7 from FIPV strain 79-1146 (FIPV-Delta 7) rendered the virus more susceptible to IFN-a 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 in trans rescued the mutant FIPV-Delta 7 from IFN sensitivity, which was not achieved by addition of 7b protein. Nevertheless, addition of protein 7a to FIPV-Delta 3 Delta 7, 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.},
  author       = {Dedeurwaerder, Annelike and Olyslaegers, Dominique and Desmarets, Lowiese and Roukaerts, Inge and Theuns, Sebastiaan and Nauwynck, Hans},
  issn         = {0022-1317},
  journal      = {JOURNAL OF GENERAL VIROLOGY},
  keywords     = {EXPRESSION,CATS,I INTERFERON,3C GENE,SPIKE PROTEIN,ENTERIC CORONAVIRUSES,INNATE IMMUNITY,CORONAVIRUS REPLICATION,ACUTE RESPIRATORY SYNDROME,PERIPHERAL-BLOOD MONOCYTES},
  language     = {eng},
  pages        = {393--402},
  title        = {ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response},
  url          = {http://dx.doi.org/10.1099/vir.0.058743-0},
  volume       = {95},
  year         = {2014},
}

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