Npro of classical swine fever virus is an antagonist of double-stranded RNA-mediated apoptosis and IFN-α/β induction

Classical swine fever virus (CSFV) protects cells from double-stranded (ds) RNA-mediated apoptosis and IFN-α/β induction. This phenotype is lost when CSFV lacks Npro (ΔNpro CSFV). In the present study, we demonstrate that Npro counteracts dsRNA-mediated apoptosis and IFN-α/β induction independently of other CSFV elements. For this purpose, we generated porcine SK-6 and PK-15 cell lines constitutively expressing Npro fused to the enhanced green fluorescent protein (EGFP). The survival of the SK6-EGFP-Npro cell line after polyinosinic polycytidylic acid [poly(IC)] treatment was comparable to that of CSFV-infected SK-6 cells and was significantly higher than the survival of the parent cell line. In PK-15 cells, the presence of EGFP-Npro prevented the ΔNpro CSFV- and poly(IC)-mediated IFN-α/β production. Importantly, Npro also inhibited IFN-α and IFN-β promoter-driven luciferase expression in human cells and blocked IFN-α/β induction mediated by Newcastle disease virus. This establishes a novel function for Npro in counteraction of the IFN-α/β induction pathway.