Archives of Virology

, Volume 158, Issue 3, pp 701–705 | Cite as

NF-κB activation by equine arteritis virus is MyD88 dependent and promotes viral replication

  • Amin Mottahedin
  • Maruthibabu Paidikondala
  • Harindranath Cholleti
  • Claudia Baule
Brief Report

Abstract

NF-κB, a family of transcription factors involved in different cell functions and immune responses is targeted by viruses. The mechanism of NF-κB signalling and its role in replication of EAV have not been investigated. We demonstrate that EAV infection in BHK-21 cells activates NF-κB, and this activation was found to be mediated through the MyD88 pathway. Infection of IKKβ−/− murine embryo fibroblasts (MEFs), which are deficient in NF-κB signalling, resulted in lower virus titre, less cytopathic effect, and reduced expression of viral proteins. These findings implicate the MyD88 pathway in EAV-induced NF-κB activation and suggest that NF-κB activation is essential for efficient replication of EAV.

Notes

Acknowledgments

This work was supported by grant 221-2006-2343 from The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas). MEFs were kindly provided by Dr. Amer Beg (Moffitt Cancer Center, USA) and Dr. Siddharth Balachandran (Fox Chase Cancer Center, USA) through Dr. Muhammad Munir. The antibody against EAV nsp3 proteins was kindly provided by Prof. Eric Snijder (LUMC, The Netherlands). The antibody against EAV N protein was kindly provided by Dr. Amy Glaser (Cornell University, USA). We thank Dr. Muhammad Munir for critically reading the manuscript and providing reagents.

Conflict of interest

The authors declare that they have no competing interests.

References

  1. 1.
    Snijder EJ, Spaan WJ (2006) Arteriviruses. In: Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1337–1355Google Scholar
  2. 2.
    Cavanagh D (1997) Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol 142:629–633PubMedGoogle Scholar
  3. 3.
    Glaser AL, de Vries AA, Rottier PJ, Horzinek MC, Colenbrander B (1996) Equine arteritis virus: a review of clinical features and management aspects. Vet Q 18:95–99PubMedCrossRefGoogle Scholar
  4. 4.
    Moore BD, Balasuriya UB, Hedges JF, MacLachlan NJ (2002) 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 298:39–44PubMedCrossRefGoogle Scholar
  5. 5.
    Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8:49–62PubMedCrossRefGoogle Scholar
  6. 6.
    Rahman MM, McFadden G (2011) Modulation of NF-kappaB signalling by microbial pathogens. Nat Rev Microbiol 9:291–306PubMedCrossRefGoogle Scholar
  7. 7.
    Lee SM, Kleiboeker SB (2005) Porcine arterivirus activates the NF-kappaB pathway through IkappaB degradation. Virology 342(1):47–59PubMedCrossRefGoogle Scholar
  8. 8.
    Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511PubMedCrossRefGoogle Scholar
  9. 9.
    Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145PubMedCrossRefGoogle Scholar
  10. 10.
    Naiki Y, Michelsent KS, Zhang W, Chen Sh, Doherty TM, Arditi M (2005) Transforming growth factor-ß differentially inhibits MyD88-dependant, but not TRAM- and TRIF-dependant, lipopolysaccharide-induced TLR4 signalling. J Biol Chem 280:5491–5495PubMedCrossRefGoogle Scholar
  11. 11.
    Seo SU, Kwon HJ, Song JH, Byun YH, Seong BL, Kawai T, Akira S, Kweon MN (2010) MyD88 signalling is indispensable for primary influenza A virus infection but dispensable for secondary infection. J Virol 84(24):12713–12722PubMedCrossRefGoogle Scholar
  12. 12.
    Fuse K, Chan G, Liu Y, Gudgeon P, Husain M, Chen M, Yeh WC, Akira S, Liu PP (2005) Myeloid differentiation factor-88 plays a crucial role in the pathogenesis of Coxsackievirus B3-induced myocarditis and influences type I interferon production. Circulation 112(15):2276–2285PubMedCrossRefGoogle Scholar
  13. 13.
    Zhong H, May MJ, Jimi E, Ghosh S (2002) The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol Cell 9(3):625–636PubMedCrossRefGoogle Scholar
  14. 14.
    Liu P, Jamaluddin M, Li K, Garofalo RP, Casola A, Brasier AR (2007) Retinoic acid-inducible gene I mediates early antiviral response and Toll-like receptor 3 expression in respiratory syncytial virus-infected airway epithelial cells. J Virol 81(3):1401–1411PubMedCrossRefGoogle Scholar
  15. 15.
    Brasier AR, Tian B, Jamaluddin M, Kalita MK, Garofalo RP, Lu M (2011) RelA Ser276 phosphorylation-coupled Lys310 acetylation controls transcriptional elongation of inflammatory cytokines in respiratory syncytial virus infection. J Virol 85(22):11752–11769PubMedCrossRefGoogle Scholar
  16. 16.
    Wang X, Hussain S, Wang EJ, Li MO, Garcia-Sastre A, Beg AA (2007) Lack of essential role of NF-kappa B p50, RelA, and cRel subunits in virus-induced type 1 IFN expression. J Immunol 178:6770–6776PubMedGoogle Scholar
  17. 17.
    Wang J, Basagoudanavar SH, Wang X, Hopewell E, Albrecht R, Garcia-Sastre A, Balachandran S, Beg AA (2010) NF-kappa B RelA subunit is crucial for early IFN-beta expression and resistance to RNA virus replication. J Immunol 185:1720–1729PubMedCrossRefGoogle Scholar
  18. 18.
    Van Kasteren PB, Beugeling C, Ninaber DK, Frias-Staheli N, Van Boheemen S, García-Sastre A, Snijder EJ, Kikkert M (2012) Arterivirus and nairovirus ovarian tumor domain-containing deubiquitinases target activated RIG-I To control innate immune signalling. J Virol 86(2):773PubMedCrossRefGoogle Scholar
  19. 19.
    Li ZW, Chu W, Hu Y, Delhase M, Deerinck T, Ellisman M, Johnson R, Karin M (1999) The IKKβeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis. J Exp Med 189(11):1839–1845PubMedCrossRefGoogle Scholar
  20. 20.
    Hiscott J, Kwon JH, Genin P (2001) Hostile takeovers: viral appropriation of the NF-kappaB pathway. J Clin Invest 107:143–151PubMedCrossRefGoogle Scholar
  21. 21.
    Kang MH, So EY, Park H, Kim BS (2008) Replication of Theiler’s virus requires NF-kappa B-activation: higher viral replication and spreading in astrocytes from susceptible mice. Glia 56(9):942–953PubMedCrossRefGoogle Scholar
  22. 22.
    Dong X, Feng H, Sun Q, Li H, Wu TT, Sun R, Tibbetts SA, Chen ZJ, Feng P (2010) Murine gamma-herpesvirus 68 hijacks MAVS and IKKβeta to initiate lytic replication. PLoS Pathog 6(7):e1001001PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  • Amin Mottahedin
    • 1
    • 2
  • Maruthibabu Paidikondala
    • 3
  • Harindranath Cholleti
    • 1
  • Claudia Baule
    • 1
  1. 1.Department of Virology, Immunobiology and ParasitologyNational Veterinary InstituteUppsalaSweden
  2. 2.Infection Biology Graduate Program, Department of Medical Biochemistry and MicrobiologyUppsala UniversityUppsalaSweden
  3. 3.Institute of BiotechnologyUniversity of HelsinkiHelsinkiFinland

Personalised recommendations