Pig BVDV-2 non-structural protein (N^pro) links to cellular antiviral response in vitro

In this study, we constructed for the first time a full-length cDNA clone of pig-original bovine viral diarrhea virus 2 (BVDV-2) strain SH-28, modified the cDNA clone (pASH28) for mutant pASHΔN^pro and derived virus strain vASHΔN^pro by deleting the genomic region encoding the N^pro polypeptide, and examined significance of protein N^pro for antiviral responses in vitro. Data showed that N^pro-deletion mutant virus vASHΔN^pro led to significant overexpression of oligo adenylate synthetase (OAS), myxovirus-resistant protein 1 (Mx1), and ubiquitin-like protein 15 (ISG15). Data also revealed that overexpression of N^pro, but not NS2 and NS3 proteins, resulted in significant down-regulation of OAS, Mx1, and ISG15 production (p ≤ 0.05) in bovine cells as well as porcine cells transfected with N^pro recombinant eukaryotic expression plasmids. N^pro (but not NS2 and NS3) was also found to inhibit poly(IC) from inducing production of type I interferon (IFN-I). These results indicated that protein N^pro may play multiple roles in regulating antiviral response in host cells interfered by pig BVDV-2 strain, and provided useful information to understand better the mechanism of BVDV-2 persistent infection in pigs.