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

Abstract

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.

Highlights

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  FMDV infection triggers PKR mRNA expression, while decreases PKR protein levels.

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  3C ^pro was responsible for FMDV-induced inhibition of PKR expression and activation.

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  3C ^pro-induced PKR reduction was independent of its proteinase activity.

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  3C ^pro induces PKR degradation by lysosomal pathway.