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Journal of Virology, November 2005, p. 14411-14420, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14411-14420.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Aurore Vidy,1 Mounira Chelbi-Alix,2 and Danielle Blondel1*

Unité Mixte de Virologie Moléculaire et Structurale UMR 2472 CNRS, UMR1157 INRA, 91198 Gif sur Yvette Cedex, France,1 UPR 9045 CNRS, Institut Lwoff, 7 rue Guy Moquet, 94801 Villejuif, France2

Received 16 June 2005/ Accepted 29 August 2005

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-{alpha}/ß) and type II (IFN-{gamma}) 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-{alpha}- and IFN-{gamma}-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.

* Corresponding author. Mailing address: Unité Mixte de Virologie Moléculaire et Structurale UMR 2472, CNRS, 91198 Gif sur Yvette Cedex, France. Phone: 33-1-69 82 38 37. Fax: 33-1-69 82 43 08. E-mail: danielle.blondel{at}vms.cnrs-gif.fr.

Journal of Virology, November 2005, p. 14411-14420, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14411-14420.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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