1887

Abstract

Porcine reproductive and respiratory syndrome, a highly infectious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), has developed various strategies to evade the host innate immune response, including the suppression of type I IFN activation. The mitochondrial antiviral signalling protein (MAVS) is an important bridging adaptor of retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 signalling pathways. Here, we demonstrated that the 3C-like protease (3CLSP) of PRRSV prevented the induction of IFN-β by cleaving MAVS in a proteasome- and caspase-independent manner. Moreover, this cleavage ability was dependent on the protease activity of 3CLSP. Mutations specifically disrupting the cysteine protease activity of 3CLSP eliminated MAVS cleavage and the inhibition of IFN induction. Subsequently, we determined that 3CLSP cleaved MAVS at Glu268. Remarkably, a MAVS point mutation at Glu268 rendered MAVS resistant to 3CLSP cleavage. These results reveal a novel PRRSV mechanism to escape host immunity by directly cleaving MAVS.

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2015-10-01
2021-10-27
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