C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-beta production.
We here report a molecular basis for downregulation of interferon (IFN)-beta production by V and C proteins of Sendai virus (SeV). The infection of HeLa cells with SeV poorly induced IFN-beta even if the expression of C/C' was disrupted. In contrast, when the expression of C/C'/Y1/Y2 or V/W was disrupted, SeV infection strongly induced IFN-beta production and significantly activated the interferon regulatory factor (IRF)-3 pathway. The independent expression of C or V inhibited the double-stranded (ds) RNA- or Newcastle disease virus (NDV)-induced activation of IRF-3 and NF-kappa B, as well as the IFN-beta promoter. This inhibitory effect was also observed when Y1, Y2, or a C-terminal half fragment (aa 85-204) of C was independently expressed. Phosphorylation and homodimer formation of IRF-3 were suppressed not only in cells infected with SeV capable of expressing both C/C'/Y1/Y2 (or Y1/Y2) and V/W, but also in HeLa cells constitutively expressing Y1. These results suggest that C, Y1, Y2, and V block signaling pathways leading to IRF-3 activation to downregulate IFN-beta production.
Komatsu
Takayuki
T
Microbiology Section, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, 910-1193, Japan.
Takeuchi
Kenji
K
Yokoo
Junko
J
Gotoh
Bin
B
D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014709:Vero Cells; D014764:Viral Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D014157:Transcription Factors; C111739:V protein, Sendai virus; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; D016899:Interferon-beta