Foot-and-mouth disease virus (FMDV) leader proteinase negatively regulates the porcine interferon-λ1 pathway.

Foot-and-mouth disease is a highly contagious viral disease caused by foot-and-mouth disease virus (FMDV) of wild and domestic cloven-hoofed animals, and causes an economically important disease in the swine industry. In this study, we found that the replication of FMDV in IBRS-2 cells could be significantly inhibited after treatment with the purified recombinant porcine interferon lambda 1 (IFN-λ1), a newly identified type III interferon. However, FMDV could not activate the IFN-λ1 promoter and IFN-λ1 mRNA expression in infected IBRS-2 cells, suggesting that FMDV has evolved mechanisms to interrupt the antiviral function of IFN-λ1. The cause of this inhibition was determined by screening all structural and non-structural proteins of FMDV, and the leader proteinase (L(pro)) was found to exhibit the highest potential to inhibit poly(I:C)-induced IFN-λ1 promoter activity. Further study revealed that the catalytic activity and a SAP (SAF-A/B, Acinus, and PIAS) domain of L(pro) were required for suppressing poly(I:C)-induced IFN-λ1 production. These data suggest that FMDV replication could be inhibited by porcine IFN-λ1, but that the virus has evolved specific mechanisms to inhibit this action.