In the present study, we demonstrated by immunostaining that the ORF120 protein, an ORFV-encoded early-late protein, localizes in both the cytoplasm and nucleus and is able to activate the NF-κB pathway in the early phase of infection by phosphorylating the IκB kinase (IKK) complex, degrading IκBα and phosphorylating and inducing the nuclear translocation of NF-κB-p65. The gene discussed is NFKBIA; the disease is infection.