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 counteracting the antiviral effect of interferon (IFN). The C protein blocks IFN signalling to prevent the activation of IFN stimulated genes. However, its underlying molecular mechanism remains to be defined.


RESULTS
Signal transducer and activator of transcription 1 (Stat1) is a critical component of IFN-alpha/beta and IFN-gamma signalling. We found that both unphosphorylated Stat1 and tyrosine-phosphorylated (pY) Stat1 were present in a form of aberrant high molecular weight complexes (HMWCs) of over 2 MDa in infected cell extracts under low-salt conditions. Of recombinant vaccinia viruses carrying each SeV gene, only those expressing the C gene induced Stat1-HMWC. SeV infected cell extracts further displayed an in vitro ability to convert the pY-Stat1 homodimer to pY-Stat1-HMWC. This cell extract 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 decomposed into smaller complexes in a high-salt buffer, and under this stringent (high-salt) condition, as well as a physiological (isotonic) condition, both unphosphorylated Stat1 and pY-Stat1 were co-precipitated with anti-C antibody.


CONCLUSIONS
The C protein physically associates with Stat1. This suggests that SeV C protein directly targets Stat1 for inhibitory control on the transcriptional activation of IFN stimulated genes.
Takeuchi
K
K
Department of Microbiology, Fukui Medical University, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Komatsu
T
T
Yokoo
J
J
Kato
A
A
Shioda
T
T
Nagai
Y
Y
Gotoh
B
B
D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000502:physiology; D011485:Protein Binding; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry* / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry* / Q000502:physiology; D014779:Virus Replication
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; D007372:Interferons