Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication

The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3 C proteinase (3C(pro)) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3C(Pro) or 3C(Pro)-induced shutoff of host protein synthesis. We show that 3C(Pro) induces PKR degradation by lysosomal pathway and no interaction is determined between 3C(Pro) and PKR. Together, our results indicate that PKR acts an important antiviral factor during FMDV infection, and FMDV has evolved a strategy to overcome PKR-mediated antiviral role by downregulation of PKR protein.