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Viruses2024; 16(8); 1240; doi: 10.3390/v16081240

Conserved Antagonization of Type I Interferon Signaling by Arterivirus GP5 Proteins.

Abstract: can establish persistent infections in animals such as equids, pigs, nonhuman primates, rodents, and possums. Some can even cause overt and severe diseases such as Equine Arteritis in horses and Porcine Reproductive and Respiratory Syndrome in pigs, leading to huge economic losses. have evolved viral proteins to antagonize the host cell's innate immune responses by inhibiting type I interferon (IFN) signaling, assisting viral evasion and persistent infection. So far, the role of the glycoprotein 5 (GP5) protein in IFN signaling inhibition remains unclear. Here, we investigated the inhibitory activity of 47 GP5 proteins derived from various hosts. We demonstrated that all GP5 proteins showed conserved activity for antagonizing TIR-domain-containing adapter proteins inducing interferon-β (TRIF)-mediated IFN-β signaling through TRIF degradation. In addition, GP5 proteins showed a conserved inhibitory activity against IFN-β signaling, induced by either pig or human TRIF. Furthermore, certain GP5 proteins could inhibit the induction of IFN-stimulated genes. These findings highlight the role of GP5 proteins in supporting persistent infection.
Publication Date: 2024-08-01 PubMed ID: 39205214PubMed Central: PMC11358952DOI: 10.3390/v16081240Google Scholar: Lookup
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  • Journal Article

Summary

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The research article reveals that all Arterivirus GP5 proteins have conserved activity in antagonizing type I interferon signaling, showing that these proteins aid in persistent viral infection.

Background

  • The virus known as Arterivirus can cause persistent infection in a diverse group of animals, leading to diseases like Equine Arteritis in horses and Porcine Reproductive and Respiratory Syndrome in pigs.
  • These diseases can significantly impact agricultural economies due to loss of livestock.
  • Arterivirus has developed ways to hinder the host cell’s innate immune responses, particularly by inhibiting type I interferon (IFN) signaling, thus aiding viral evasion and persistent infection.
  • So far, the role of Arterivirus glycoprotein 5 (GP5) protein in this inhibition process remained unclear, initiating the significance of the study.

Methodology

  • The team investigated the inhibitory activity in 47 Arterivirus GP5 proteins taken from a wide range of hosts.
  • The research study used TRIF, or TIR-domain-containing adapter proteins inducing interferon-β, for testing the GP5 proteins’ antagonistic activity.
  • Both pig and human TRIF were used to gauge the inhibitory activity against IFN-β signaling by the GP5 proteins.

Findings

  • The study found that all of the 47 GP5 proteins from Arterivirus demonstrated conserved activity in antagonizing TRIF-mediated IFN-β signaling due to TRIF degradation.
  • This antagonistic activity is universally inhibitory against IFN-β signaling, as confirmed by both pig and human TRIF inducements.
  • Further, it was discovered that some GP5 proteins could inhibit the induction of interferon-stimulated genes, highlighting GP5 proteins’ role in maintaining persistent viral infections.

Implications

  • This research provides valuable insights into how Arterivirus remains persistent in hosts by employing GP5 proteins to weaken the immune response.
  • The findings may potentially lead to the development of novel antiviral strategies by targeting this GP5-mediated interference of immune signaling.

Cite This Article

APA
Ringo RS, Choonnasard A, Okabayashi T, Saito A. (2024). Conserved Antagonization of Type I Interferon Signaling by Arterivirus GP5 Proteins. Viruses, 16(8), 1240. https://doi.org/10.3390/v16081240

Publication

ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 16
Issue: 8
PII: 1240

Researcher Affiliations

Ringo, Rissar Siringo
  • Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.
  • Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
Choonnasard, Amonrat
  • Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.
  • Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
Okabayashi, Tamaki
  • Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.
  • Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
  • Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan.
Saito, Akatsuki
  • Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.
  • Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
  • Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan.

MeSH Terms

  • Animals
  • Signal Transduction
  • Arterivirus / genetics
  • Arterivirus / metabolism
  • Humans
  • Swine
  • Interferon Type I / metabolism
  • Arterivirus Infections / veterinary
  • Arterivirus Infections / virology
  • Arterivirus Infections / immunology
  • Interferon-beta / metabolism
  • Interferon-beta / genetics
  • Immunity, Innate
  • Viral Proteins / metabolism
  • Viral Proteins / genetics
  • HEK293 Cells

Grant Funding

  • JP24fk0410047, JP24fk0410056, and JP24fk0410058, JP22fk0108511, JP22fk0108506 / Japan Agency for Medical Research and Development (AMED)
  • JP24K09227, JPJSBP120245706, JP22H02500, JP21H02361, JP23K20041 / JSPS
  • n/a / G-7 Grant
  • R5 KEN77, R6 KEN119 / Ito Foundation Research Grant

Conflict of Interest Statement

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

This article includes 49 references
  1. Vanmechelen B, Vergote V, Laenen L, Koundouno FR, Bore JA, Wada J, Kuhn JH, Carroll MW, Maes P. Expanding the Arterivirus Host Spectrum: Olivier’s Shrew Virus 1, A Novel Arterivirus Discovered in African Giant Shrews. Sci. Rep. 2018;8:11171.
    doi: 10.1038/s41598-018-29560-xpmc: PMC6057926pubmed: 30042503google scholar: lookup
  2. Brinton MA, Gulyaeva AA, Balasuriya UBR, Dunowska M, Faaberg KS, Goldberg T, Leung FCC, Nauwynck HJ, Snijder EJ, Stadejek T. ICTV Virus Taxonomy Profile: Arteriviridae 2021. J. Gen. Virol. 2021;102:001632.
    doi: 10.1099/jgv.0.001632pmc: PMC8513641pubmed: 34356005google scholar: lookup
  3. Zhang M, Li X, Deng Z, Chen Z, Liu Y, Gao Y, Wu W, Chen Z. Structural Biology of the Arterivirus Nsp11 Endoribonucleases. J. Virol. 2016;91:e01309-16.
    doi: 10.1128/JVI.01309-16pmc: PMC5165224pubmed: 27795409google scholar: lookup
  4. Guo R, Yan X, Li Y, Cui J, Misra S, Firth AE, Snijder EJ, Fang Y. A Swine Arterivirus Deubiquitinase Stabilizes Two Major Envelope Proteins and Promotes Production of Viral Progeny. PLoS Pathog. 2021;17:e1009403.
  5. Brinton MA, Snijder EJ. Arteriviruses. Encyclopedia of Virology 3rd ed. Academic Press; Oxford, UK: 2008. pp. 176–186.
  6. Wu F, Peng K, Tian J, Xu X, Zhou E, Chen H. Immune Response to Fc Tagged GP5 Glycoproteins of Porcine Reproductive and Respiratory Syndrome Virus. Viral Immunol. 2014;27:343–349.
    doi: 10.1089/vim.2014.0041pubmed: 25014350google scholar: lookup
  7. Ammann CG, Messer RJ, Peterson KE, Hasenkrug KJ. Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells. PLoS ONE 2009;4:e6105.
  8. Balasuriya UBR, Go YY, MacLachlan NJ. Equine Arteritis Virus. Vet. Microbiol. 2013;167:93–122.
  9. Zhang Z, Li Z, Li H, Yang S, Ren F, Bian T, Sun L, Zhou B, Zhou L, Qu X. The Economic Impact of Porcine Reproductive and Respiratory Syndrome Outbreak in Four Chinese Farms: Based on Cost and Revenue Analysis. Front. Vet. Sci. 2022;9:1024720.
    doi: 10.3389/fvets.2022.1024720pmc: PMC9597626pubmed: 36311672google scholar: lookup
  10. Lauck M, Alkhovsky SV, Bào Y, Bailey AL, Shevtsova ZV, Shchetinin AM, Vishnevskaya TV, Lackemeyer MG, Postnikova E, Mazur S. Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused by Distinct Arteriviruses. J. Virol. 2015;89:8082–8087.
    doi: 10.1128/JVI.01046-15pmc: PMC4505640pubmed: 25972539google scholar: lookup
  11. Dunowska M, Biggs PJ, Zheng T, Perrott MR. Identification of a Novel Nidovirus Associated with a Neurological Disease of the Australian Brushtail Possum (Trichosurus vulpecula). Vet. Microbiol. 2012;156:418–424.
  12. Anderson GW, Rowland RR, Palmer GA, Even C, Plagemann PG. Lactate Dehydrogenase-Elevating Virus Replication Persists in Liver, Spleen, Lymph Node, and Testis Tissues and Results in Accumulation of Viral RNA in Germinal Centers, Concomitant with Polyclonal Activation of B Cells. J. Virol. 1995;69:5177–5185.
  13. Allende R, Laegreid WW, Kutish GF, Galeota JA, Wills RW, Osorio FA. Porcine Reproductive and Respiratory Syndrome Virus: Description of Persistence in Individual Pigs upon Experimental Infection. J. Virol. 2000;74:10834–10837.
  14. Vatter HA, Donaldson EF, Huynh J, Rawlings S, Manoharan M, Legasse A, Planer S, Dickerson MF, Lewis AD, Colgin LMA. A Simian Hemorrhagic Fever Virus Isolate from Persistently Infected Baboons Efficiently Induces Hemorrhagic Fever Disease in Japanese Macaques. Virology 2015;474:186–198.
    doi: 10.1016/j.virol.2014.10.018pmc: PMC4304765pubmed: 25463617google scholar: lookup
  15. Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Cook RF, Timoney PJ, Balasuriya UBR. Equine Arteritis Virus Long-Term Persistence Is Orchestrated by CD8+ T Lymphocyte Transcription Factors, Inhibitory Receptors, and the CXCL16/CXCR6 Axis. PLoS Pathog. 2019;15:e1007950.
  16. Jian Z, Ma R, Zhu L, Deng H, Li F, Zhao J, Deng L, Lai S, Sun X, Tang H. Evasion of Interferon-Mediated Immune Response by Arteriviruses. Front. Immunol. 2022;13:963923.
    doi: 10.3389/fimmu.2022.963923pmc: PMC9454096pubmed: 36091073google scholar: lookup
  17. Schneider WM, Chevillotte MD, Rice CM. Interferon-Stimulated Genes: A Complex Web of Host Defenses. Annu. Rev. Immunol. 2014;32:513–545.
  18. Li D, Wu M. Pattern Recognition Receptors in Health and Diseases. Sig. Transduct. Target Ther. 2021;6:291.
    doi: 10.1038/s41392-021-00687-0pmc: PMC8333067pubmed: 34344870google scholar: lookup
  19. Kawai T, Akira S. The Role of Pattern-Recognition Receptors in Innate Immunity: Update on Toll-like Receptors. Nat. Immunol. 2010;11:373–384.
    doi: 10.1038/ni.1863pubmed: 20404851google scholar: lookup
  20. Singh H, Koury J, Kaul M. Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System. Viruses 2021;13:170.
    doi: 10.3390/v13020170pmc: PMC7912342pubmed: 33498715google scholar: lookup
  21. McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A. Type I Interferons in Infectious Disease. Nat. Rev. Immunol. 2015;15:87–103.
    doi: 10.1038/nri3787pmc: PMC7162685pubmed: 25614319google scholar: lookup
  22. Perng Y-C, Lenschow DJ. ISG15 in Antiviral Immunity and Beyond. Nat. Rev. Microbiol. 2018;16:423–439.
    doi: 10.1038/s41579-018-0020-5pmc: PMC7097117pubmed: 29769653google scholar: lookup
  23. Lerolle S, Freitas N, Cosset F-L, Legros V. Host Cell Restriction Factors of Bunyaviruses and Viral Countermeasures. Viruses 2021;13:784.
    doi: 10.3390/v13050784pmc: PMC8146327pubmed: 33925004google scholar: lookup
  24. Huang C, Zhang Q, Guo X, Yu Z, Xu A-T, Tang J, Feng W. Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 4 Antagonizes Beta Interferon Expression by Targeting the NF-κB Essential Modulator. J. Virol. 2014;88:10934–10945.
    doi: 10.1128/JVI.01396-14pmc: PMC4178863pubmed: 25008936google scholar: lookup
  25. Chen J, Wang D, Sun Z, Gao L, Zhu X, Guo J, Xu S, Fang L, Li K, Xiao S. Arterivirus Nsp4 Antagonizes Interferon Beta Production by Proteolytically Cleaving NEMO at Multiple Sites. J. Virol. 2019;93:10-1128.
    doi: 10.1128/JVI.00385-19pmc: PMC6613749pubmed: 30944180google scholar: lookup
  26. Wang T-Y, Sun M-X, Zhang H-L, Wang G, Zhan G, Tian Z-J, Cai X-H, Su C, Tang Y-D. Evasion of Antiviral Innate Immunity by Porcine Reproductive and Respiratory Syndrome Virus. Front. Microbiol. 2021;12:693799.
    doi: 10.3389/fmicb.2021.693799pmc: PMC8430839pubmed: 34512570google scholar: lookup
  27. 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. J. Virol. 2012;86:3839–3850.
    doi: 10.1128/JVI.06466-11pmc: PMC3302520pubmed: 22258253google scholar: lookup
  28. Niwa H, Yamamura K-I, Myiazaki J-I. Efficient Selection for High-Expression Transfectants with a Novel Eukaryotic Vector. Gene 1991;108:193–199.
    doi: 10.1016/0378-1119(91)90434-Dpubmed: 1660837google scholar: lookup
  29. Gentili M, Kowal J, Tkach M, Satoh T, Lahaye X, Conrad C, Boyron M, Lombard B, Durand S, Kroemer G. Transmission of Innate Immune Signaling by Packaging of cGAMP in Viral Particles. Science 2015;349:1232–1236.
    doi: 10.1126/science.aab3628pubmed: 26229115google scholar: lookup
  30. Choonnasard A, Shofa M, Okabayashi T, Saito A. Conserved Functions of Orthohepadnavirus X Proteins to Inhibit Type-I Interferon Signaling. Int. J. Mol. Sci. 2024;25:3753.
    doi: 10.3390/ijms25073753pmc: PMC11011558pubmed: 38612565google scholar: lookup
  31. Zhu J, Smith K, Hsieh PN, Mburu YK, Chattopadhyay S, Sen GC, Sarkar SN. High-Throughput Screening for TLR3–IFN Regulatory Factor 3 Signaling Pathway Modulators Identifies Several Antipsychotic Drugs as TLR Inhibitors. J. Immunol. 2010;184:5768–5776.
    doi: 10.4049/jimmunol.0903559pmc: PMC2874113pubmed: 20382888google scholar: lookup
  32. Kasza L, Shadduck JA, Christofinis GJ. Establishment, Viral Susceptibility and Biological Characteristics of a Swine Kidney Cell Line SK-6. Res. Vet. Sci. 1972;13:46–53.
    doi: 10.1016/S0034-5288(18)34087-6pubmed: 4336054google scholar: lookup
  33. Shofa M, Saito A. Generation of Porcine PK-15 Cells Lacking the Ifnar1 or Stat2 Gene to Optimize the Efficiency of Viral Isolation. PLoS ONE 2023;18:e0289863.
  34. Vats A, Gautam D, Maharana J, Singh Chera J, Kumar S, Rout PK, Werling D, De S. Poly I:C Stimulation in-Vitro as a Marker for an Antiviral Response in Different Cell Types Generated from Buffalo (Bubalus bubalis). Mol. Immunol. 2020;121:136–143.
    doi: 10.1016/j.molimm.2020.03.004pubmed: 32200171google scholar: lookup
  35. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ. Differential Roles of MDA5 and RIG-I Helicases in the Recognition of RNA Viruses. Nature 2006;441:101–105.
    doi: 10.1038/nature04734pubmed: 16625202google scholar: lookup
  36. Xiong Z, Niu X, Song Y, Su D, Wang F, Chen R, He D. Evolution of Porcine Reproductive and Respiratory Syndrome Virus GP5 and GP3 Genes under swIFN-β Immune Pressure and Interferon Regulatory Factor-3 Activation Suppressed by GP5. Res. Vet. Sci. 2015;101:175–179.
    doi: 10.1016/j.rvsc.2015.05.007pubmed: 26022070google scholar: lookup
  37. Han M, Kim CY, Rowland RRR, Fang Y, Kim D, Yoo D. Biogenesis of Non-Structural Protein 1 (Nsp1) and Nsp1-Mediated Type I Interferon Modulation in Arteriviruses. Virology 2014;458–459:136–150.
    doi: 10.1016/j.virol.2014.04.028pubmed: 24928046google scholar: lookup
  38. Beura LK, Sarkar SN, Kwon B, Subramaniam S, Jones C, Pattnaik AK, Osorio FA. Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1beta Modulates Host Innate Immune Response by Antagonizing IRF3 Activation. J. Virol. 2010;84:1574–1584.
    doi: 10.1128/JVI.01326-09pmc: PMC2812326pubmed: 19923190google scholar: lookup
  39. Li H, Zheng Z, Zhou P, Zhang B, Shi Z, Hu Q, Wang H. The Cysteine Protease Domain of Porcine Reproductive and Respiratory Syndrome Virus Non-Structural Protein 2 Antagonizes Interferon Regulatory Factor 3 Activation. J. Gen. Virol. 2010;91:2947–2958.
    doi: 10.1099/vir.0.025205-0pubmed: 20826620google scholar: lookup
  40. Sun Y, Ke H, Han M, Chen N, Fang W, Yoo D. Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus Suppresses Both MAVS and RIG-I Expression as One of the Mechanisms to Antagonize Type I Interferon Production. PLoS ONE 2016;11:e0168314.
  41. Shi X, Wang L, Li X, Zhang G, Guo J, Zhao D, Chai S, Deng R. Endoribonuclease Activities of Porcine Reproductive and Respiratory Syndrome Virus Nsp11 Was Essential for Nsp11 to Inhibit IFN-β Induction. Mol. Immunol. 2011;48:1568–1572.
  42. Warren CJ, Yu S, Peters DK, Barbachano-Guerrero A, Yang Q, Burris BL, Worwa G, Huang I-C, Wilkerson GK, Goldberg TL. Primate Hemorrhagic Fever-Causing Arteriviruses Are Poised for Spillover to Humans. Cell 2022;185:3980–3991.e18.
    doi: 10.1016/j.cell.2022.09.022pmc: PMC9588614pubmed: 36182704google scholar: lookup
  43. Han M, Yoo D. Modulation of Innate Immune Signaling by Nonstructural Protein 1 (Nsp1) in the Family Arteriviridae. Virus Res. 2014;194:100.
  44. Assavacheep P, Thanawongnuwech R. Porcine Respiratory Disease Complex: Dynamics of Polymicrobial Infections and Management Strategies after the Introduction of the African Swine Fever. Front. Vet. Sci. 2022;9:1048861.
    doi: 10.3389/fvets.2022.1048861pmc: PMC9732666pubmed: 36504860google scholar: lookup
  45. Zhao D, Yang B, Yuan X, Shen C, Zhang D, Shi X, Zhang T, Cui H, Yang J, Chen X. Advanced Research in Porcine Reproductive and Respiratory Syndrome Virus Co-Infection with Other Pathogens in Swine. Front. Vet. Sci. 2021;8:699561.
    doi: 10.3389/fvets.2021.699561pmc: PMC8426627pubmed: 34513970google scholar: lookup
  46. Zhang J, Wang P, Xie C, Ha Z, Shi N, Zhang H, Li Z, Han J, Xie Y, Qiu X. Synergistic Pathogenicity by Coinfection and Sequential Infection with NADC30-like PRRSV and PCV2 in Post-Weaned Pigs. Viruses 2022;14:193.
    doi: 10.3390/v14020193pmc: PMC8877551pubmed: 35215787google scholar: lookup
  47. Luo Q, Zheng Y, Zhang H, Yang Z, Sha H, Kong W, Zhao M, Wang N. Research Progress on Glycoprotein 5 of Porcine Reproductive and Respiratory Syndrome Virus. Animals 2023;13:813.
    doi: 10.3390/ani13050813pmc: PMC10000246pubmed: 36899670google scholar: lookup
  48. Butler JE, Lager KM, Golde W, Faaberg KS, Sinkora M, Loving C, Zhang YI. Porcine Reproductive and Respiratory Syndrome (PRRS): An Immune Dysregulatory Pandemic. Immunol. Res. 2014;59:81.
    doi: 10.1007/s12026-014-8549-5pmc: PMC7091131pubmed: 24981123google scholar: lookup
  49. Zheng Q, Chen D, Li P, Bi Z, Cao R, Zhou B, Chen P. Co-Expressing GP5 and M Proteins under Different Promoters in Recombinant Modified Vaccinia Virus Ankara (rMVA)-Based Vaccine Vector Enhanced the Humoral and Cellular Immune Responses of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). Virus Genes 2007;35:585.
    doi: 10.1007/s11262-007-0161-5pmc: PMC7088781pubmed: 17922181google scholar: lookup

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