Paramyxovirus C protein targets the host interferon (IFN) system for virus immune evasion. To identify its unknown anti-IFN activity, we examined the effect of Sendai virus C protein on activation of the IFN-α promoter via various signaling pathways. This study uncovers a novel ability of C protein to block Toll-like receptor (TLR) 7- and TLR9-dependent IFN-α induction, which is specific to plasmacytoid dendritic cells. C protein interacts with a serine/threonine kinase IKKα and inhibits phosphorylation of IRF7. This anti-IFN activity of C protein is shared across genera of the Paramyxovirinae, and thus appears to play an important role in paramyxovirus immune evasion.
Keywords: C protein; ELISA; IFN; IFN-stimulated genes; IFN-β promoter stimulator-1; IKKα; IPS-1; IRAK1; IRF; ISGs; Interferon-α; IκB kinase alpha; MDA5; MeV; MyD88; N; NiV; Nipah virus; ORF; P; PAMPs; PIVs; PKR; Paramyxovirus; RIG-I; RIG-I-like receptors; RLRs; SDS; SeV; Sendai virus; TIR-domain-containing adapter-inducing interferon-β; TLR; TLR7; TRAF6; TRIF; Toll-like receptor; bPIV3; bovine PIV type 3; double stranded; ds; enzyme-linked immunosorbent assay; interferon; interferon regulatory factor; interleukin-1 receptor-associated kinase 1; mAb; measles virus; melanoma differentiation-associated gene 5; monoclonal antibody; myeloid differentiation factor 88; nucleocapsid protein; open reading frame; pAb; pDC; pDCs; parainfluenza viruses; pathogen-associated molecular patterns; phosphoprotein; plasmacytoid dendritic cells; polyclonal antibody; protein kinase R; retinoic acid-inducible gene-I; sodium dodecyl sulfate; tumor necrosis factor receptor-associated 6.
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