This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bauhofer, O.
Right arrow Articles by Ruggli, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bauhofer, O.
Right arrow Articles by Ruggli, N.

 Previous Article  |  Next Article 

Journal of Virology, April 2007, p. 3087-3096, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02032-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Classical Swine Fever Virus Npro Interacts with Interferon Regulatory Factor 3 and Induces Its Proteasomal Degradation{triangledown}

Oliver Bauhofer,1 Artur Summerfield,1 Yoshihiro Sakoda,2 Jon-Duri Tratschin,1 Martin A. Hofmann,1 and Nicolas Ruggli1*

Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland,1 Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan2

Received 17 September 2006/ Accepted 29 December 2006

Viruses have evolved a multitude of strategies to subvert the innate immune system by interfering with components of the alpha/beta interferon (IFN-{alpha}/ß) induction and signaling pathway. It is well established that the pestiviruses prevent IFN-{alpha}/ß induction in their primary target cells, such as epitheloidal and endothelial cells, macrophages, and conventional dendritic cells, a phenotype mediated by the viral protein Npro. Central players in the IFN-{alpha}/ß induction cascade are interferon regulatory factor 3 (IRF3) and IRF7. Recently, it was proposed that classical swine fever virus (CSFV), the porcine pestivirus, induced the loss of IRF3 by inhibiting the transcription of IRF3 mRNA. In the present study, we show that endogenous IRF3 and IRF3 expressed from a cytomegalovirus (CMV) promoter are depleted in the presence of CSFV by means of Npro, while CSFV does not inhibit CMV promoter-driven protein expression. We also demonstrate that CSFV does not reduce the transcriptional activity of the IRF3 promoter and does not affect the stability of IRF3 mRNA. In fact, CSFV Npro induces proteasomal degradation of IRF3, as demonstrated by proteasome inhibition studies. Furthermore, Npro coprecipitates with IRF3, suggesting that the proteasomal degradation of IRF3 is induced by a direct or indirect interaction with Npro. Finally, we show that Npro does not downregulate IRF7 expression.

* Corresponding author. Mailing address: Institute of Virology and Immunoprophylaxis (IVI), Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland. Phone: 0041 31 848 9211. Fax: 0041 31 848 9222. E-mail: nicolas.ruggli{at}ivi.admin.ch.

{triangledown} Published ahead of print on 10 January 2007.

Journal of Virology, April 2007, p. 3087-3096, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02032-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tews, B. A., Schurmann, E.-M., Meyers, G. (2009). Mutation of Cysteine 171 of Pestivirus Erns RNase Prevents Homodimer Formation and Leads to Attenuation of Classical Swine Fever Virus. J. Virol. 83: 4823-4834 [Abstract] [Full Text]  
  • Ruggli, N., Summerfield, A., Fiebach, A. R., Guzylack-Piriou, L., Bauhofer, O., Lamm, C. G., Waltersperger, S., Matsuno, K., Liu, L., Gerber, M., Choi, K. H., Hofmann, M. A., Sakoda, Y., Tratschin, J.-D. (2009). Classical Swine Fever Virus Can Remain Virulent after Specific Elimination of the Interferon Regulatory Factor 3-Degrading Function of Npro. J. Virol. 83: 817-829 [Abstract] [Full Text]  
  • Magkouras, I., Matzener, P., Rumenapf, T., Peterhans, E., Schweizer, M. (2008). RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by Erns of pestiviruses. J. Gen. Virol. 89: 2501-2506 [Abstract] [Full Text]  
  • Gallei, A., Blome, S., Gilgenbach, S., Tautz, N., Moennig, V., Becher, P. (2008). Cytopathogenicity of Classical Swine Fever Virus Correlates with Attenuation in the Natural Host. J. Virol. 82: 9717-9729 [Abstract] [Full Text]  
  • Everett, R. D., Young, D. F., Randall, R. E., Orr, A. (2008). STAT-1- and IRF-3-Dependent Pathways Are Not Essential for Repression of ICP0-Null Mutant Herpes Simplex Virus Type 1 in Human Fibroblasts. J. Virol. 82: 8871-8881 [Abstract] [Full Text]  
  • Doceul, V., Charleston, B., Crooke, H., Reid, E., Powell, P. P., Seago, J. (2008). The Npro product of classical swine fever virus interacts with I{kappa}B{alpha}, the NF-{kappa}B inhibitor. J. Gen. Virol. 89: 1881-1889 [Abstract] [Full Text]  
  • Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]  
  • de los Santos, T., Diaz-San Segundo, F., Grubman, M. J. (2007). Degradation of Nuclear Factor Kappa B during Foot-and-Mouth Disease Virus Infection. J. Virol. 81: 12803-12815 [Abstract] [Full Text]  
  • Tews, B. A., Meyers, G. (2007). The Pestivirus Glycoprotein Erns Is Anchored in Plane in the Membrane via an Amphipathic Helix. J. Biol. Chem. 282: 32730-32741 [Abstract] [Full Text]  
  • Seago, J., Hilton, L., Reid, E., Doceul, V., Jeyatheesan, J., Moganeradj, K., McCauley, J., Charleston, B., Goodbourn, S. (2007). The Npro product of classical swine fever virus and bovine viral diarrhea virus uses a conserved mechanism to target interferon regulatory factor-3. J. Gen. Virol. 88: 3002-3006 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»