Foot-and-Mouth Disease Virus Inhibits RIP2 Protein Expression to Promote Viral Replication

Receptors interaction protein 2 (RIP2) is a specific adaptor molecule in the downstream of NOD2. The role of RIP2 during foot-and-mouth disease virus (FMDV) infection remains unknown. Here, our results showed that RIP2 inhibited FMDV replication and played an important role in the activation of IFN-beta and NF-B signal pathways during FMDV infection. FMDV infection triggered RIP2 transcription, while it reduced the expression of RIP2 protein. Detailed analysis showed that FMDV 2B, 2C, 3C(pro), and L-pro proteins were responsible for inducing the reduction of RIP2 protein. 3C(pro) and L-pro are viral proteinases that can induce the cleavage or reduction of many host proteins and block host protein synthesis. The carboxyl terminal 105-114 and 135-144 regions of 2B were essential for reduction of RIP2. Our results also showed that the N terminal 1-61 region of 2C were essential for the reduction of RIP2. The 2C-induced reduction of RIP2 was dependent on inducing the reduction of poly(A)-binding protein 1 (PABPC1). The interaction between RIP2 and 2C was observed in the context of viral infection, and the residues 1-61 were required for the interaction. These data clarify novel mechanisms of reduction of RIP2 mediated by FMDV.

Automated summary

The study found that RIP2 inhibited the replication of foot-and-mouth disease virus (FMDV) and played an important role in the activation of the IFN-β and NF-κB signal pathways during FMDV infection. Specific regions of FMDV proteins were responsible for reducing RIP2 protein expression, with specific regions of 2B and 2C being crucial for this process.