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.
FOOTNOTES
- Received 16 June 2005.
- Accepted 29 August 2005.
- ↵*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.
- American Society for Microbiology
