Rabies virus P protein interacts with STAT1 and inhibits interferon signal transduction pathways.
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/beta) 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.
Vidy
Aurore
A
Unité Mixte de Virologie Moléculaire et Structurale UMR 2472, CNRS, 91198 Gif sur Yvette Cedex, France.
Chelbi-Alix
Mounira
M
Blondel
Danielle
D
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D007372:Interferons / Q000502:physiology*; D018832:Molecular Chaperones; D009447:Neuroblastoma; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011820:Rabies virus / Q000201:enzymology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D014162:Transfection; D015678:Viral Structural Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D011994:Recombinant Proteins; D015678:Viral Structural Proteins; D007372:Interferons; D012321:DNA-Directed RNA Polymerases