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https://doi.org/10.53941/jiim.2025.100006
Yoon, M., Lee, S., Song, D., Hwang, J., Kim, H., Yoo, H., Choi, M., & Kim, S. Antiviral Activity of Gallus Recombinant Interferon α3. Journal of Inflammatory and Infectious Medicine. 2025, 1(1), 6. doi: https://doi.org/10.53941/jiim.2025.100006
Volume 1, Issue 1, 2025
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Article

Antiviral Activity of Gallus Recombinant Interferon α3

Myungdal Yoon 1, Seungheon Lee 1, Donghwan Song 1, Jihyung Hwang 2, HeeJoon Kim 1, Hyun Yoo 2, Mijeong Choi 2,3, and Sinae Kim 4,*

1 College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea

2 Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 
Seoul 05029, Republic of Korea

3 Biomedical Engineering Research Institute, 32 Dongguk-ro, Goyang-si 10326, Republic of Korea

4 The Institute of YbdY biotechnology, 83, Gasan digital 1-ro, Geumcheon-gu, Seoul 08589, Republic of Korea

* Correspondence: seconeco@naver.com; Tel.: +82-2-457-0868; Fax: +82-2-2030-7788

Received: 10 September 2024; Revised: 24 January 2025; Accepted: 10 March 2025; Published: 12 March 2025

Abstract: Interferons (IFNs) were first discovered in 1957 in a nutrient fluid from chick chorioallantois membranes, where it was observed that administration of virus stimulated interferon production in many animals, tissues, and cells, within a short time. They are classified into type 1, type 2, and IFN-like cytokines, with type 1 IFN classified into IFNα, IFNβ, IFNε, IFNκ, IFNω, IFNδ, and IFNτ. Clinical tests for recombinant human IFNs and bovine IFNτ have been conducted since 1981. Although infections of Highly Pathogenic Avian Influenza Virus (HPAI) have continued to cause high economic losses in poultry industry causing many deaths of poultry, few molecular experiments based on gallus (ga) IFNs have been reported since 1994 and clinical trials to test their use are limited. Here, we examined the activities of newly produced three recombinant gaIFNα3s on different species of cells. The recombinant gaIFNα3s showed significant antiviral activity in Gallus embryo fibroblast (GEF) cells, showing good potential to prevent the cytopathic effect of vesicular stomatitis virus (VSV). However, they failed to protect Wistar Institute Susan Hayflick (WISH) cells, Madin-Darby bovine kidney epithelial (MDBK) cells, and Madin-Darby canine epithelial-like (MDCK) cells. This study demonstrated the impact of species specificity on the antiviral activity of gaIFNα3 and the effect of location of fusion protein.

Keywords:

interferons recombinant protein gallus gallus embryo fibroblast antiviral activity

References

  1. Isaacs, A.; Lindenmann, J. Virus interference. I. The interferon. Proc. R. Soc. Lond. B Biol. Sci. 1957, 147, 258–267.
  2. Krause, C.D.; Pestka, S. Historical developments in the research of interferon receptors. Cytokine Growth Factor. Rev. 2007, 18, 473–482.
  3. Pestka, S. The interferons: 50 years after their discovery, there is much more to learn. J. Biol. Chem. 2007, 282, 20047–20051.
  4. Pestka, S. The human interferon alpha species and receptors. Biopolymers 2000, 55, 254–287.
  5. Pestka, S.; Krause, C.D.; Walter, M.R. Interferons, interferon-like cytokines, and their receptors. Immunol. Rev. 2004, 202, 8–32.
  6. Fu, X.Y.; Schindler, C.; Improta, T.; Aebersold, R.; Darnell, J.E., Jr. The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc. Natl. Acad. Sci. USA 1992, 89, 7840–7843.
  7. Schindler, C.; Fu, X.Y.; Improta, T.; Aebersold, R.; Darnell, J.E., Jr. Proteins of transcription factor ISGF-3: One gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc. Natl. Acad. Sci. USA 1992, 89, 7836–7839.
  8. Taniguchi, T.; Takaoka, A. The interferon-alpha/beta system in antiviral responses: A multimodal machinery of gene regulation by the IRF family of transcription factors. Curr. Opin. Immunol. 2002, 14, 111–116.
  9. Su, L.; David, M. Distinct mechanisms of STAT phosphorylation via the interferon-alpha/beta receptor. Selective inhibition of STAT3 and STAT5 by piceatannol. J. Biol. Chem. 2000, 275, 12661–12666.
  10. Goossens, K.E.; Ward, A.C.; Lowenthal, J.W.; Bean, A.G. Chicken interferons, their receptors and interferon-stimulated genes. Dev. Comp. Immunol. 2013, 41, 370–376.
  11. Zhang, Y.; Fu, D.; Chen, H.; Zhang, Z.; Shi, Q.; Elsayed, A.K.; Li, B. Partial antiviral activities detection of chicken Mx jointing with neuraminidase gene (NA) against Newcastle disease virus. PLoS ONE 2013, 8, e71688.
  12. Qu, H.; Yang, L.; Meng, S.; Xu, L.; Bi, Y.; Jia, X.; Li, J.; Sun, L.; Liu, W. The differential antiviral activities of chicken interferon alpha (ChIFN-alpha) and ChIFN-beta are related to distinct interferon-stimulated gene expression. PLoS ONE 2013, 8, e59307.
  13. Santhakumar, D.; Rubbenstroth, D.; Martinez-Sobrido, L.; Munir, M. Avian Interferons and Their Antiviral Effectors. Front. Immunol. 2017, 8, 49.
  14. Simancas-Racines, A.; Cadena-Ullauri, S.; Guevara-Ramirez, P.; Zambrano, A.K.; Simancas-Racines, D. Avian Influenza: Strategies to Manage an Outbreak. Pathogens 2023, 12, 610.
  15. Kanaujia, R.; Bora, I.; Ratho, R.K.; Thakur, V.; Mohi, G.K.; Thakur, P. Avian influenza revisited: Concerns and constraints. Virusdisease 2022, 33, 456–465.
  16. Sekellick, M.J.; Ferrandino, A.F.; Hopkins, D.A.; Marcus, P.I. Chicken interferon gene: Cloning, expression, and analysis. J. Interferon Res. 1994, 14, 71–79.
  17. Suresh, M.; Karaca, K.; Foster, D.; Sharma, J.M. Molecular and functional characterization of turkey interferon. J. Virol. 1995, 69, 8159–8163.
  18. Schultz, U.; Kock, J.; Schlicht, H.J.; Staeheli, P. Recombinant duck interferon: A new reagent for studying the mode of interferon action against hepatitis B virus. Virology 1995, 212, 641–649.
  19. Li, H.T.; Ma, B.; Mi, J.W.; Jin, H.Y.; Xu, L.N.; Wang, J.W. Cloning, in vitro expression and bioactivity of goose interferon-alpha. Cytokine 2006, 34, 177–183.
  20. Tian, L.; Zhao, P.; Ma, B.; Guo, G.; Sun, Y.; Xing, M. Cloning, expression and antiviral bioactivity of red-crowned crane interferon-alpha. Gene 2014, 544, 49–55.
  21. Kim, E.; Jhun, H.; Kim, J.; Park, U.; Jo, S.; Kwak, A.; Kim, S.; Nguyen, T.T.; Kang, Y.; Choi, I.; et al. Species Specific Antiviral Activity of Porcine Interferon-alpha8 (IFNalpha8). Immune Netw. 2017, 17, 424–436.
  22. Kang, D.; Ryoo, S.; Chung, B.; Lee, J.; Park, S.; Han, J.; Jeong, S.; Rho, G.; Hong, J.; Bae, S.; et al. Amino acid differences in interferon-tau (IFN-tau) of Bos taurus Coreanae and Holstein. Cytokine 2012, 59, 273–279.
  23. Gokul, A.; Arumugam, T.; Ramsuran, V. Genetic Ethnic Differences in Human 2'-5'-Oligoadenylate Synthetase and Disease Associations: A Systematic Review. Genes 2023, 14, 527.
  24. Tag-El-Din-Hassan, H.T.; Sasaki, N.; Torigoe, D.; Morimatsu, M.; Agui, T. Analysis of the Relationship Between Enzymatic and Antiviral Activities of the Chicken Oligoadenylate Synthetase-Like. J. Interferon Cytokine Res. 2017, 37, 71–80.
  25. Wang, S.; Xu, Z.; Liu, Y.; Yu, M.; Zhang, T.; Liu, P.; Qi, X.; Chen, Y.; Meng, L.; Guo, R.; et al. OASL suppresses infectious bursal disease virus replication by targeting VP2 for degrading through the autophagy pathway. J. Virol. 2024, 98, e00181-24.
  26. Del Vesco, A.P.; Jang, H.J.; Monson, M.S.; Lamont, S.J. Role of the chicken oligoadenylate synthase-like gene during in vitro Newcastle disease virus infection. Poult. Sci. 2021, 100, 101067.
  27. Zav'yalov, V.P.; Hamalainen-Laanaya, H.; Korpela, T.K.; Wahlroos, T. Interferon-Inducible Myxovirus Resistance Proteins: Potential Biomarkers for Differentiating Viral from Bacterial Infections. Clin. Chem. 2019, 65, 739–750.
  28. Haller, O.; Kochs, G.; Weber, F. Interferon, Mx, and viral countermeasures. Cytokine Growth Factor. Rev. 2007, 18, 425–433.
  29. Haller, O.; Staeheli, P.; Kochs, G. Interferon-induced Mx proteins in antiviral host defense. Biochimie 2007, 89, 812–818.
  30. Kochs, G.; Janzen, C.; Hohenberg, H.; Haller, O. Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes. Proc. Natl. Acad. Sci. USA 2002, 99, 3153–3158.
  31. Kochs, G.; Haener, M.; Aebi, U.; Haller, O. Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers. J. Biol. Chem. 2002, 277, 14172–14176.
  32. Schutz, A.; Bernhard, F.; Berrow, N.; Buyel, J.F.; Ferreira-da-Silva, F.; Haustraete, J.; van den Heuvel, J.; Hoffmann, J.E.; de Marco, A.; Peleg, Y.; et al. A concise guide to choosing suitable gene expression systems for recombinant protein production. STAR Protoc. 2023, 4, 102572.
  33. Jaffe, S.R.; Strutton, B.; Levarski, Z.; Pandhal, J.; Wright, P.C. Escherichia coli as a glycoprotein production host: Recent developments and challenges. Curr. Opin. Biotechnol. 2014, 30, 205–210.
  34. Dey, P.; Ahuja, A.; Panwar, J.; Choudhary, P.; Rani, S.; Kaur, M.; Sharma, A.; Kaur, J.; Yadav, A.K.; Sood, V.; et al. Immune Control of Avian Influenza Virus Infection and Its Vaccine Development. Vaccines 2023, 11, 593.
  35. Samuel, C.E. Antiviral actions of interferons. Clin. Microbiol. Rev. 2001, 14, 778–809.
  36. Pavlovic, J.; Zurcher, T.; Haller, O.; Staeheli, P. Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein. J. Virol. 1990, 64, 3370–3375.