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 Brzózka, K.
Right arrow Articles by Conzelmann, K.-K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brzózka, K.
Right arrow Articles by Conzelmann, K.-K.

 Previous Article  |  Next Article 

Journal of Virology, March 2006, p. 2675-2683, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2675-2683.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inhibition of Interferon Signaling by Rabies Virus Phosphoprotein P: Activation-Dependent Binding of STAT1 and STAT2

Krzysztof Brzózka, Stefan Finke, and Karl-Klaus Conzelmann*

Max von Pettenkofer Institute and Gene Center, Ludwig-Maximilians-University, D-81377 Munich, Germany

Received 27 October 2005/ Accepted 21 December 2005

Rabies virus (RV) phosphoprotein P is an interferon (IFN) antagonist counteracting transcriptional activation of type I IFN (K. Brzózka, S. Finke, and K. K. Conzelmann, J. Virol 79:7673-7681, 2005). We here show that RV P in addition is responsible for preventing IFN-{alpha}/ß- and IFN-{gamma}-stimulated JAK-STAT signaling in RV-infected cells by the retention of activated STATs in the cytoplasm. Expression of IFN-stimulated response element- and gamma-activated sequence-controlled genes was severely impaired in cells infected with RV SAD L16 or in cells expressing RV P protein from transfected plasmids. In contrast, a recombinant RV expressing small amounts of P had lost the ability to interfere with JAK-STAT signaling. IFN-mediated tyrosine phosphorylation of STAT1 and STAT2 was not impaired in RV P-expressing cells; rather, a defect in STAT recycling was suggested by distinct accumulation of tyrosine-phosphorylated STATs in cell extracts. In the presence of P, activated STAT1 and STAT2 were unable to accumulate in the nucleus. Notably, STAT1 and STAT2 were coprecipitated with RV P only from extracts of cells previously stimulated with IFN-{alpha} or IFN-{gamma}, whereas in nonstimulated cells no association of P with STATs was observed. This conditional, IFN activation-dependent binding of tyrosine-phosphorylated STATs by RV P is unique for a viral IFN antagonist. The 10 C-terminal residues of P are required for counteracting JAK-STAT signaling but not for inhibition of transcriptional activation of IFN-ß, thus demonstrating two independent functions of RV P in counteracting the host's IFN response.

* Corresponding author. Mailing address: Max von Pettenkofer Institute and Gene Center, Feodor Lynen Str. 25, D-81377 Munich, Germany, Phone: 49 89 2180 76851. Fax: 49 89 2180 76899. E-mail: conzelma{at}lmb.uni-muenchen.de.

Journal of Virology, March 2006, p. 2675-2683, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2675-2683.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Castel, G., Chteoui, M., Caignard, G., Prehaud, C., Mehouas, S., Real, E., Jallet, C., Jacob, Y., Ruigrok, R. W. H., Tordo, N. (2009). Peptides That Mimic the Amino-Terminal End of the Rabies Virus Phosphoprotein Have Antiviral Activity. J. Virol. 83: 10808-10820 [Abstract] [Full Text]  
  • Moseley, G. W., Lahaye, X., Roth, D. M., Oksayan, S., Filmer, R. P., Rowe, C. L., Blondel, D., Jans, D. A. (2009). Dual modes of rabies P-protein association with microtubules: a novel strategy to suppress the antiviral response. J. Cell Sci. 122: 3652-3662 [Abstract] [Full Text]  
  • Ciancanelli, M. J., Volchkova, V. A., Shaw, M. L., Volchkov, V. E., Basler, C. F. (2009). Nipah Virus Sequesters Inactive STAT1 in the Nucleus via a P Gene-Encoded Mechanism. J. Virol. 83: 7828-7841 [Abstract] [Full Text]  
  • Marschalek, A., Finke, S., Schwemmle, M., Mayer, D., Heimrich, B., Stitz, L., Conzelmann, K.-K. (2009). Attenuation of Rabies Virus Replication and Virulence by Picornavirus Internal Ribosome Entry Site Elements. J. Virol. 83: 1911-1919 [Abstract] [Full Text]  
  • Pfaller, C. K., Conzelmann, K.-K. (2008). Measles Virus V Protein Is a Decoy Substrate for I{kappa}B Kinase {alpha} and Prevents Toll-Like Receptor 7/9-Mediated Interferon Induction. J. Virol. 82: 12365-12373 [Abstract] [Full Text]  
  • Habjan, M., Penski, N., Spiegel, M., Weber, F. (2008). T7 RNA polymerase-dependent and -independent systems for cDNA-based rescue of Rift Valley fever virus. J. Gen. Virol. 89: 2157-2166 [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]  
  • Wu, M., Xu, Y., Lin, S., Zhang, X., Xiang, L., Yuan, Z. (2007). Hepatitis B virus polymerase inhibits the interferon-inducible MyD88 promoter by blocking nuclear translocation of Stat1. J. Gen. Virol. 88: 3260-3269 [Abstract] [Full Text]  
  • Vidy, A., El Bougrini, J., Chelbi-Alix, M. K., Blondel, D. (2007). The Nucleocytoplasmic Rabies Virus P Protein Counteracts Interferon Signaling by Inhibiting both Nuclear Accumulation and DNA Binding of STAT1. J. Virol. 81: 4255-4263 [Abstract] [Full Text]  
  • Hornung, V., Ellegast, J., Kim, S., Brzozka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K., Schlee, M., Endres, S., Hartmann, G. (2006). 5'-Triphosphate RNA Is the Ligand for RIG-I. Science 314: 994-997 [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»