C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-β production

Abstract

We here report a molecular basis for downregulation of interferon (IFN)-β production by V and C proteins of Sendai virus (SeV). The infection of HeLa cells with SeV poorly induced IFN-β 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-β 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-κB, as well as the IFN-β 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-β production. © 2004 Elsevier Inc. All rights reserved.