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Home / Equine Research Bank / Biomed Res Int / Equine arteritis virus does not induce interferon production...
BioMed research international2014; 2014; 420658; doi: 10.1155/2014/420658

Equine arteritis virus does not induce interferon production in equine endothelial cells: identification of nonstructural protein 1 as a main interferon antagonist.

Abstract: The objective of this study was to investigate the effect of equine arteritis virus (EAV) on type I interferon (IFN) production. Equine endothelial cells (EECs) were infected with the virulent Bucyrus strain (VBS) of EAV and expression of IFN-β was measured at mRNA and protein levels by quantitative real-time RT-PCR and IFN bioassay using vesicular stomatitis virus expressing the green fluorescence protein (VSV-GFP), respectively. Quantitative RT-PCR results showed that IFN-β mRNA levels in EECs infected with EAV VBS were not increased compared to those in mock-infected cells. Consistent with quantitative RT-PCR, Sendai virus- (SeV-) induced type I IFN production was inhibited by EAV infection. Using an IFN-β promoter-luciferase reporter assay, we subsequently demonstrated that EAV nsps 1, 2, and 11 had the capability to inhibit type I IFN activation. Of these three nsps, nsp1 exhibited the strongest inhibitory effect. Taken together, these data demonstrate that EAV has the ability to suppress the type I IFN production in EECs and nsp1 may play a critical role to subvert the equine innate immune response.
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Publication Date: 2014-05-25 PubMed ID: 24967365PubMed Central: PMC4055586DOI: 10.1155/2014/420658Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article investigates how equine arteritis virus (EAV) impacts type I interferon (IFN) production, and suggested that the virus suppresses IFN production and employs its nonstructural protein 1 (nsp1) as an important tool to subvert the equine innate immune response.

Study Objective and Methodology

  • The main aim of the study was to understand the impact of equine arteritis virus (EAV) on type I interferon (IFN) production in equine endothelial cells (EECs).
  • To test this, the researchers infected EECs with the Bucyrus strain (VBS) of EAV and then examined the resulting quantitative real-time RT-PCR and IFN bioassay using vesicular stomatitis virus expressing the green fluorescence protein (VSV-GFP) to track the cells’ IFN-β expressions.

Results and Findings

  • The study found that EECs infected with EAV Bucyrus strain did not demonstrate an increase in IFN-β mRNA levels compared to uninfected cells (Mock infected cells).
  • The production of type I IFN, induced by Sendai virus (SeV), was found to be inhibited following EAV infection.
  • A subsequent IFN-β promoter-luciferase reporter assay revealed that three nonstructural proteins of EAV – nsps 1, 2, and 11 – exhibited inhibitory capabilities against type I IFN activation. Out of these proteins, nsp1 showed the strongest inhibitory effect.

Conclusion

  • The research concludes that EAV possesses an ability to suppress the production of type I IFN in EECs. This suggests a possible method by which the virus circumvents the equine innate immune response.
  • The most significant finding is the role of nonstructural protein 1 (nsp1), which appears to play a significant role in subverting the equine immune response. It could potentially be a key target for interventions designed to enhance the innate immune response in horses.

Cite This Article

APA
Go YY, Li Y, Chen Z, Han M, Yoo D, Fang Y, Balasuriya UB. (2014). Equine arteritis virus does not induce interferon production in equine endothelial cells: identification of nonstructural protein 1 as a main interferon antagonist. Biomed Res Int, 2014, 420658. https://doi.org/10.1155/2014/420658

Publication

BioMed research international
ISSN: 2314-6141
NlmUniqueID: 101600173
Country: United States
Language: English
Volume: 2014
Pages: 420658

Researcher Affiliations

Go, Yun Young
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA ; Virus Research and Testing Group, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon 305-343, Republic of Korea.
Li, Yanhua
  • Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506, USA.
Chen, Zhenhai
  • Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Han, Mingyuan
  • Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Yoo, Dongwan
  • Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Fang, Ying
  • Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506, USA.
Balasuriya, Udeni B R
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.

MeSH Terms

  • Animals
  • Arterivirus Infections / genetics
  • Arterivirus Infections / immunology
  • Arterivirus Infections / metabolism
  • Arterivirus Infections / veterinary
  • Cricetinae
  • Endothelial Cells
  • Equartevirus / genetics
  • Equartevirus / immunology
  • Equartevirus / metabolism
  • HEK293 Cells
  • Horses
  • Humans
  • Immunity, Innate
  • Interferon-beta / antagonists & inhibitors
  • Interferon-beta / biosynthesis
  • Interferon-beta / genetics
  • Interferon-beta / immunology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism

References

This article includes 68 references
  1. Balasuriya UB, Go YY, Maclachlan NJ. Equine arteritis virus. Veterinary Microbiology 2013;167(1-2):93–122.
    pmc: PMC7126873pubmed: 23891306
  2. Timoney PJ, McCollum WH. Equine viral arteritis. The Veterinary Clinics of North America 1993;9(2):295–309.
    pmc: PMC7134676pubmed: 8395325
  3. Cavanagh D. Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Archives of Virology 1997;142:629–633.
    pubmed: 9349308
  4. Snijder EJ, Kikkert M, Fang Y. Arterivirus molecular biology and pathogenesis. Journal of General Virology 2013;94:2141–2163.
    pubmed: 23939974
  5. Snijder EJ, Meulenberg JJM. The molecular biology of arteriviruses. Journal of General Virology 1998;79(5):961–979.
    pubmed: 9603311
  6. Firth AE, Zevenhoven-Dobbe JC, Wills NM. Discovery of a small arterivirus gene that overlaps the gp5 coding sequence and is important for virus production. Journal of General Virology 2011;92(5):1097–1106.
    pmc: PMC3139419pubmed: 21307223
  7. Snijder EJ. Arteriviruses. Fields Virology 2001. pp. 1205–1220.
  8. den Boon JA, Snijder EJ, Chirnside ED, de Vries AAF, Horzinek MC, Spaan WJM. Equine arteritis virus is not a togavirus but belongs to the coronaviruslike superfamily. Journal of Virology 1991;65(6):2910–2920.
    pmc: PMC240924pubmed: 1851863
  9. van Aken D, Zevenhoven-Dobbe J, Gorbalenya AE, Snijder EJ. Proteolytic maturation of replicase polyprotein pp1a by the nsp4 main proteinase is essential for equine arteritis virus replication and includes internal cleavage of nsp7. Journal of General Virology 2006;87(12):3473–3482.
    pubmed: 17098961
  10. Ziebuhr J, Snijder EJ, Gorbalenya AE. Virus-encoded proteinases and proteolytic processing in the Nidovirales. Journal of General Virology 2000;81(4):853–879.
    pubmed: 10725411
  11. de Vries AAF, Chirnside ED, Horzinek MC, Rottier PJM. Structural proteins of equine arteritis virus. Journal of Virology 1992;66(11):6294–6303.
    pmc: PMC240121pubmed: 1328669
  12. Snijder EJ, van Tol H, Pedersen KW, Raamsman MJB, de Vries AAF. Identification of a novel structural protein of arteriviruses. Journal of Virology 1999;73(8):6335–6345.
    pmc: PMC112712pubmed: 10400725
  13. Wieringa R, de Vries AAF, Raamsman MJB, Rottier PJM. Characterization of two new structural glycoproteins, GP3 and GP4, of equine arteritis virus. Journal of Virology 2002;76(21):10829–10840.
    pmc: PMC136612pubmed: 12368326
  14. Randall RE, Goodbourn S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. Journal of General Virology 2008;89(1):1–47.
    pubmed: 18089727
  15. Luo R, Xiao S, Jiang Y. Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon-β production by interfering with the RIG-I signaling pathway. Molecular Immunology 2008;45(10):2839–2846.
    pmc: PMC7112510pubmed: 18336912
  16. Thanos D, Maniatis T. Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome. Cell 1995;83(7):1091–1100.
    pubmed: 8548797
  17. Bí¶®rt W, van Reeth K, Pensaert M. In vivo and in vitro interferon (IFN) studies with the porcine reproductive and respiratory syndrome virus (PRRSV). Advances in Experimental Medicine and Biology 1998;440:461–467.
    pubmed: 9782316
  18. Choi C, Cho W-S, Kim B, Chae C. Expression of interferon-gamma and tumour necrosis factor-alpha in pigs experimentally infected with porcine reproductive and respiratory syndrome virus (PRRSV). Journal of Comparative Pathology 2002;127(2-3):106–113.
    pubmed: 12354520
  19. Rowland RRR, Robinson B, Stefanick J. Inhibition of porcine reproductive and respiratory syndrome virus by interferon-gamma and recovery of virus replication with 2-aminopurine. Archives of Virology 2001;146(3):539–555.
    pmc: PMC7087212pubmed: 11338389
  20. Wan J, Wu W, Xia C. Expression of porcine interferon-gamma gene in Pichia pastoris and its effect of inhibiting porcine reproductive and respiratory syndrome virus. Sheng Wu Gong Cheng Xue Bao 2002;18(6):683–686.
    pubmed: 12674637
  21. Chang H, Jeng C, Liu JJ. Reduction of porcine reproductive and respiratory syndrome virus (PRRSV) infection in swine alveolar macrophages by porcine circovirus 2 (PCV2)-induced interferon-alpha. Veterinary Microbiology 2005;108(3-4):167–177.
    pmc: PMC7117408pubmed: 15936905
  22. Wesley RD, Lager KM, Kehrli ME. Jr.. Infection with Porcine reproductive and respiratory syndrome virus stimulates an early gamma interferon response in the serum of pigs. Canadian Journal of Veterinary Research 2006;70(3):176–182.
    pmc: PMC1477926pubmed: 16850939
  23. Chung H-K, Lee J-H, Kim S-H, Chae C. Expression of interferon-α and Mx1 protein in pigs acutely infected with porcine reproductive and respiratory syndrome virus (PRRSV). Journal of Comparative Pathology 2004;130(4):299–305.
    pubmed: 15053933
  24. Meier WA, Galeota J, Osorio FA, Husmann RJ, Schnitzlein WM, Zuckermann FA. Gradual development of the interferon-γ response of swine to porcine reproductive and respiratory syndrome virus infection or vaccination. Virology 2003;309(1):18–31.
    pubmed: 12726723
  25. Miller LC, Laegreid WW, Bono JL, Chitko-McKown CG, Fox JM. Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells. Archives of Virology 2004;149(12):2453–2463.
    pmc: PMC7087254pubmed: 15338318
  26. Beura LK, Sarkar SN, Kwon B. Porcine reproductive and respiratory syndrome virus nonstructural protein 1β modulates host innate immune response by antagonizing IRF3 activation. Journal of Virology 2010;84(3):1574–1584.
    pmc: PMC2812326pubmed: 19923190
  27. Beura LK, Subramaniam S, Vu HL, Kwon B, Pattnaik AK, Osorio FA. Identification of amino acid residues important for anti-IFN activity of porcine reproductive and respiratory syndrome virus non-structural protein 1. Virology 2012;433:431–439.
    pmc: PMC7111991pubmed: 22995188
  28. Fang Y, Fang L, Wang Y. Porcine reproductive and respiratory syndrome virus nonstructural protein 2 contributes to NF-kappaB activation. Virology Journal 2012;9(article 83).
    pmc: PMC3443020pubmed: 22546080
  29. Jung K, Renukaradhya GJ, Alekseev KP, Fang Y, Tang Y, Saif LJ. Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections. Journal of General Virology 2009;90(11):2713–2723.
    pmc: PMC2862479pubmed: 19656969
  30. Li Y, Zhu L, Lawson SR, Fang Y. Targeted mutations in a highly conserved motif of the nsp1beta protein impair the interferon antagonizing activity of porcine reproductive and respiratory syndrome virus. Journal of General Virology 2013;94:1972–1983.
    pubmed: 23761406
  31. Subramaniam S, Kwon B, Beura LK, Kuszynski CA, Pattnaik AK, Osorio FA. Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-κB and Sp1. Virology 2010;406(2):270–279.
    pubmed: 20701940
  32. Sun Z, Li Y, Ransburgh R, Snijder EJ, Fang Y. Nonstructural protein 2 of porcine reproductive and respiratory syndrome virus inhibits the antiviral function of interferon-stimulated gene 15. Journal of Virology 2012;86:3839–3850.
    pmc: PMC3302520pubmed: 22258253
  33. Niwa H, Yamamura K, Miyazaki J. Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 1991;108(2):193–199.
    pubmed: 1660837
  34. van Kasteren PB, Bailey-Elkin BA, James TW. Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells. Proceedings of the National Academy of Sciences of the United States of America 2013;110:E838–E847.
    pmc: PMC3587229pubmed: 23401522
  35. van Kasteren PB, Beugeling C, Ninaber DK. Arterivirus and nairovirus ovarian tumor domain-containing deubiquitinases target activated RIG-I to control innate immune signaling. Journal of Virology 2012;86(2):773–785.
    pmc: PMC3255818pubmed: 22072774
  36. Hedges JF, Demaula CD, Moore BD, Mclaughlin BE, Simon SI, James Maclachlan N. Characterization of equine E-selectin. Immunology 2001;103(4):498–504.
    pmc: PMC1783268pubmed: 11529941
  37. Moore BD, Balasuriya UBR, Hedges JF, MacLachlan NJ. Growth characteristics of a highly virulent, a moderately virulent, and an avirulent strain of equine arteritis virus in primary equine endothelial cells are predictive of their virulence to horses. Virology 2002;298(1):39–44.
    pubmed: 12093171
  38. Sever JL. Application of a microtechnique to viral serological investigations. The Journal of Immunology 1962;88:320–329.
    pubmed: 13910995
  39. Dalton KP, Rose JK. Vesicular stomatitis virus glycoprotein containing the entire green fluorescent protein on its cytoplasmic domain is incorporated efficiently into virus particles. Virology 2001;279(2):414–421.
    pubmed: 11162797
  40. Go YY, Snijder EJ, Timoney PJ, Balasuriya UBR. Characterization of equine humoral antibody response to the nonstructural proteins of equine arteritis virus. Clinical and Vaccine Immunology 2011;18(2):268–279.
    pmc: PMC3067362pubmed: 21147938
  41. Balasuriya UBR, Snijder EJ, Heidner HW. Development and characterization of an infectious cDNA clone of the virulent Bucyrus strain of Equine arteritis virus. Journal of General Virology 2007;88(3):918–924.
    pubmed: 17325365
  42. Yoneyama M, Suhara W, Fukuhara Y, Sato M, Ozato K, Fujita T. Autocrine amplification of type I interferon gene expression mediated by interferon stimulated gene factor 3 (ISGF3). The Journal of Biochemistry 1996;120:160–169.
    pubmed: 8864859
  43. Komatsu T, Takeuchi K, Gotoh B. Bovine parainfluenza virus type 3 accessory proteins that suppress beta interferon production. Microbes and Infection 2007;9(8):954–962.
    pubmed: 17548221
  44. Overend C, Mitchell R, He D, Rompato G, Grubman MJ, Garmendia AE. Recombinant swine beta interferon protects swine alveolar macrophages and MARC-145 cells from infection with Porcine reproductive and respiratory syndrome virus. Journal of General Virology 2007;88(3):925–931.
    pubmed: 17325366
  45. MacLachlan NJ, Balasuriya UB, Rossitto PV, Hullinger PA, Patton JF, Wilson WD. Fatal experimental equine arteritis virus infection of a pregnant mare: immunohistochemical staining of viral antigens. Journal of Veterinary Diagnostic Investigation 1996;8:367–374.
    pubmed: 8844583
  46. Wagner HM, Balasuriya UBR, MacLachlan NJ. The serologic response of horses to equine arteritis virus as determined by competitive enzyme-linked immunosorbent assays (c-ELISAs) to structural and non-structural viral proteins. Comparative Immunology, Microbiology and Infectious Diseases 2003;26(4):251–260.
    pubmed: 12676125
  47. Snijder EJ, Wassenaar ALM, Spaan WJM. Proteolytic processing of the replicase ORF1a protein of equine arteritis virus. Journal of Virology 1994;68(9):5755–5764.
    pmc: PMC236979pubmed: 8057457
  48. Pedersen KW, van der Meer Y, Roos N, Snijder EJ. Open reading frame 1a-encoded subunits of the arterivirus replicase induce endoplasmic reticulum-derived double-membrane vesicles which carry the viral replication complex. Journal of Virology 1999;73(3):2016–2026.
    pmc: PMC104444pubmed: 9971782
  49. van Dinten LC, Wassenaar AL, Gorbalenya AE, Spaan WJ, Snijder EJ. Processing of the equine arteritis virus replicase ORF1b protein: identification of cleavage products containing the putative viral polymerase and helicase domains. Journal of Virology 1996;70:6625–6633.
    pmc: PMC190703pubmed: 8794297
  50. Ramakers C, Ruijter JM, Deprez RH, Moorman AFM. Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neuroscience Letters 2003;339(1):62–66.
    pubmed: 12618301
  51. Kim O, Sun Y, Lai FW, Song C, Yoo D. Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells. Virology 2010;402(2):315–326.
    pmc: PMC7157927pubmed: 20416917
  52. Solórzano A, Webby RJ, Lager KM, Janke BH, García-Sastre A, Richt JA. Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. Journal of Virology 2005;79(12):7535–7543.
    pmc: PMC1143661pubmed: 15919908
  53. Haller O, Weber F. Pathogenic viruses: smart manipulators of the interferon system. Current Topics in Microbiology and Immunology 2007;316:315–334.
    pmc: PMC7120724pubmed: 17969454
  54. Samuel CE. Antiviral actions of interferons. Clinical Microbiology Reviews 2001;14(4):778–809.
    pmc: PMC89003pubmed: 11585785
  55. Ramanan P, Shabman RS, Brown CS, Amarasinghe GK, Basler CF, Leung DW. Filoviral immune evasion mechanisms. Viruses 2011;3(9):1634–1649.
    pmc: PMC3187693pubmed: 21994800
  56. Albina E, Carrat C, Charley B. Interferon-α response to swine arterivirus (PoAV), the porcine reproductive and respiratory syndrome virus. Journal of Interferon and Cytokine Research 1998;18(7):485–490.
    pubmed: 9712364
  57. Basler CF. Nipah and hendra virus interactions with the innate immune system. Current Topics in Microbiology and Immunology 2012;359:123–152.
    pubmed: 22491899
  58. Totura AL, Baric RS. SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Current Opinion in Virology 2012;2:264–275.
    pmc: PMC7102726pubmed: 22572391
  59. Frias-Staheli N, Giannakopoulos NV, Kikkert M. Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell Host and Microbe 2007;2(6):404–416.
    pmc: PMC2184509pubmed: 18078692
  60. Nedialkova DD, Ulferts R, van den Born E. Biochemical characterization of arterivirus nonstructural protein 11 reveals the nidovirus-wide conservation of a replicative endoribonuclease. Journal of Virology 2009;83(11):5671–5682.
    pmc: PMC2681944pubmed: 19297500
  61. Shi X, Wang L, Li X. Endoribonuclease activities of porcine reproductive and respiratory syndrome virus nsp11 was essential for nsp11 to inhibit IFN-β induction. Molecular Immunology 2011;48(12-13):1568–1572.
    pmc: PMC7112683pubmed: 21481939
  62. Go YY, Cook RF, Fulgêncio JQ. Assessment of correlation between in vitro CD3+ T cell susceptibility to EAV infection and clinical outcome following experimental infection. Veterinary Microbiology 2012;157(1-2):220–225.
    pubmed: 22177968
  63. Han M, Du Y, Song C, Yoo D. Degradation of CREB-binding protein and modulation of type I interferon induction by the zinc finger motif of the porcine reproductive and respiratory syndrome virus nsp1alpha subunit. Virus Research 2013;172:54–65.
    pubmed: 23287061
  64. Yoo D, Song C, Sun Y, Du Y, Kim O, Liu H. Modulation of host cell responses and evasion strategies for porcine reproductive and respiratory syndrome virus. Virus Research 2010;154(1-2):48–60.
    pmc: PMC7114477pubmed: 20655963
  65. Shi X, Wang L, Zhi Y. Porcine reproductive and respiratory syndrome virus (PRRSV) could be sensed by professional beta interferon-producing system and had mechanisms to inhibit this action in MARC-145 cells. Virus Research 2010;153(1):151–156.
    pmc: PMC7114505pubmed: 20692306
  66. Shi X, Zhang G, Wang L. The nonstructural protein 1 papain-like cysteine protease was necessary for porcine reproductive and respiratory syndrome virus nonstructural protein 1 to inhibit interferon-β induction. DNA and Cell Biology 2011;30(6):355–362.
    pubmed: 21438756
  67. Song C, Krell P, Yoo D. Nonstructural protein 1α subunit-based inhibition of NF-κB activation and suppression of interferon-β production by porcine reproductive and respiratory syndrome virus. Virology 2010;407(2):268–280.
    pubmed: 20850164
  68. Tijms MA, van der Meer Y, Snijder EJ. Nuclear localization of non-structural protein 1 and nucleocapsid protein of equine arteritis virus. Journal of General Virology 2002;83(4):795–800.
    pubmed: 11907328
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