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Virus-Cell Interactions | Spotlight

Rabies Virus P Protein Interacts with STAT1 and Inhibits Interferon Signal Transduction Pathways

Aurore Vidy, Mounira Chelbi-Alix, Danielle Blondel
Aurore Vidy
1Unité Mixte de Virologie Moléculaire et Structurale UMR 2472 CNRS, UMR1157 INRA, 91198 Gif sur Yvette Cedex, France
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Mounira Chelbi-Alix
2UPR 9045 CNRS, Institut Lwoff, 7 rue Guy Moquet, 94801 Villejuif, France
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Danielle Blondel
1Unité Mixte de Virologie Moléculaire et Structurale UMR 2472 CNRS, UMR1157 INRA, 91198 Gif sur Yvette Cedex, France
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  • For correspondence: danielle.blondel@vms.cnrs-gif.fr
DOI: 10.1128/JVI.79.22.14411-14420.2005
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ABSTRACT

Rabies virus P protein is a cofactor of RNA polymerase. We investigated other potential roles of P (CVS strain) by searching for cellular partners using two-hybrid screening. We isolated a cDNA encoding the signal transducer and activator of transcription 1 (STAT1) that is a critical component of interferon type I (IFN-α/β) and type II (IFN-γ) signaling. We confirmed this interaction by glutathione S-transferase-pull-down assay. Deletion mutant analysis indicated that the carboxy-terminal part of P interacted with a region containing the DNA-binding domain and the coiled-coil domain of STAT1. The expression of P protein inhibits IFN-α- and IFN-γ-induced transcriptional responses, thus impairing the IFN-induced antiviral state. Mechanistic studies indicate that P protein does not induce STAT1 degradation and does not interfere with STAT1 phosphorylation but prevents IFN-induced STAT1 nuclear accumulation. These results indicate that rabies P protein overcomes the antiviral response of the infected cells.

  • Copyright © 2005 American Society for Microbiology
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Rabies Virus P Protein Interacts with STAT1 and Inhibits Interferon Signal Transduction Pathways
Aurore Vidy, Mounira Chelbi-Alix, Danielle Blondel
Journal of Virology Oct 2005, 79 (22) 14411-14420; DOI: 10.1128/JVI.79.22.14411-14420.2005

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Rabies Virus P Protein Interacts with STAT1 and Inhibits Interferon Signal Transduction Pathways
Aurore Vidy, Mounira Chelbi-Alix, Danielle Blondel
Journal of Virology Oct 2005, 79 (22) 14411-14420; DOI: 10.1128/JVI.79.22.14411-14420.2005
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KEYWORDS

interferons
Phosphoproteins
Signal Transduction
viral structural proteins

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