摘要

Type I interferons are major components of the innate immune response of hosts, and accordingly, many viruses have evolved mechanisms to modulate the host response during infection. Bovine viral diarrhea virus (BVDV) nonstructural protein N-pro and structural protein E-rns play important roles in inhibiting type I interferon. The aim of this study was to explore the epistatic effects of amino acid mutations in N-pro and E-rns in porcine ST cells to characterize the immune response induced by BVDV-2. Plasmids with mutant amino acids His49 (H49), Glu22 (E22) in N-pro, and His300 (H300), Lys412 (K412) in E-rns which had been changed to Alanine (A) had similar effects on type I interferon production in MDBK and ST cells, but resulted in much greater ISG15, OAS, and Mx production in ST cells. The rescued vASH/N(pro)H49E(rns)K412 virus showed the best efficiency with respect to modulating antiviral cytokines, indicating that the amino acids N-pro H49 and E-rns K412 had highly synergistic effects in abolishing the ability to inhibit type I interferon. These findings have importance practical implications owing to the increasing prevalence of BVDV infections, including persistent infections, in domestic pigs.