In this study, we provided evidences that the IHNV NV possesses capability for down-regulation of the host IFN system: (a) NV-knockout mutant rIHNV induced greater expressions of the IFN1 and Mx1 genes than the wild-type rIHNV in RTG-2 cells; (b) RTG-2 cells infected with NV-knockout rIHNV produced a higher level of IFN1 activity in cell culture supernatant relative to wild-type rIHNV; (c) wild-type rIHNV more efficiently blocked the expressions of IFN1 and Mx1 than the NV-knockout mutant rIHNV in RTG-2 cells treated with poly I∶C after viral infection. The gene discussed is IFNA1; the disease is viral infectious disease.