The VP1 Protein of Porcine Teschovirus Inhibits the Innate Immune Response to Viral Infection by Blocking MDA5 Activation.

Porcine teschovirus (PTV) can cause reproductive dysfunction and respiratory diseases, with high mortality rates for sick pigs. Among Picornaviridae family virus-encoded proteins, the VP1 structural protein is critical for viral immune evasion. However, whether PTV VP1 inhibits the type I interferon (IFN) response remains unknown. Here, it shows that the PTV VP1 protein significantly hinders the activation of NF-κB, impairing Sendai virus-induced expression of beta IFN (IFN-β). Further studies revealed that VP1 targets and interacts with the MDA5 factor in the RIG-I like receptors pathway. More importantly, the VP1 protein interacts with the caspase activation and recruitment domain and Hel domains of MDA5, blocking IFN-β expression. Our findings provide evidence about the VP1 protein of PTV hinders MDA5 activation and may represent a viral mechanism to escape the innate immune response.