Sendai virus C protein physically associates with Stat1

Background: The P/C gene of the Sendai virus (SeV), a member of the family Paramyxoviridae, encodes C protein, which plays a crucial role in counterac ting the antiviral effect of interferon (IFN). The C protein blocks IFN sig nalling to prevent the activation of IFN stimulated genes. However, its und erlying molecular mechanism remains to be defined. Results: Signal transducer and activator of transcription 1 (Stat1) is a cr itical component of IFN-alpha/beta and IFN-gamma signalling. We found that both unphosphorylated Stat1 and tyrosine-phosphorylated (pY) Stat1 were pre sent in a form of aberrant high molecular weight complexes (HMWCs) of over 2MDa in infected cell extracts under low-salt conditions. Of recombinant va ccinia viruses carrying each SeV gene, only those expressing the C gene ind uced Stat1-HMWC. SeV infected cell extracts further displayed an in vitro a bility to convert the pY-Stat1 homodimer to pY-Stat1-HMWC. This cell extrac t activity was not seen after removal of the C protein from the extracts. C protein was therefore involved in the formation of HMWCs. The HMWCs decomp osed into smaller complexes in a high-salt buffer, and under this stringent (high-salt) condition, as well as a physiological (isotonic) condition, bo th unphosphorylated Stat1 and pY-Stat1 were co-precipitated with anti-C ant ibody. Conclusion: The C protein physically associates with Stat1. This suggests t hat SeV C protein directly targets Stat1 for inhibitory control on the tran scriptional activation of IFN stimulated genes.