Disruption of interferon-β production by the N(pro) of atypical porcine pestivirus

Atypical porcine pestivirus (APPV) is an emerging porcine virus that threatens global swine production. Pestiviruses can prevent interferon (IFN) production to avoid the host innate immune response, and the N(pro) viral protein can play a critical role. Knowledge of the host immune response to APPV infection is limited. Here, we showed that the IFN-β production was suppressed by APPV-N(pro) and the IFN regulatory factor 3 (IRF3) promoter activity stimulated by adaptor molecules of the IFN-β signaling pathway was also inhibited in the APPV-N(pro)-expressed cells. The APPV-N(pro) was able to interact with IRF3 and interfere the phosphorylation of IRF3, indicated that the IFN-β antagonism of APPV-N(pro) mainly depended on blocking IRF3 activity. To identify the functional region of APPV-N(pro), a panel of truncated APPV-N(pro) was constructed, and its influence on the IRF3 activation was investigated. The results showed that the N-terminal 31–51 amino acids of APPV-N(pro) were mainly associated with inhibition of the IFN-β response. Taken together, this is the first study focusing on elucidating the function of APPV protein by revealing a novel mechanism of N(pro) in disruption of host IFN-β production, which will enlighten future study in addressing APPV pathogenesis and immune evasion.