The cis-responsive element of Foot-and-mouth disease virus interacts with host cellular factor PCBP2 dependent on host specificity

I. Background: Foot-and-mouth disease virus (FMDV) is a highly contagious viral pathogen in cloven-hoofed animal including cattle and pig, yet progress in the molecular mechanisms of FMDV genome replication is notably lagging behind that for many RNA viruses. A positive single stranded RNA of FMDV encodes a single long open reading frame flanked by a long 5’-untranslated region (5’UTR) and a short 3’-UTR. The cis-responsive element (CRE) of 5’UTR is critical for FMDV genome replication. II. Methods and Results: Here, we described that poly(C)-binding protein 2 (PCBP2) is revealed as a CRE-binding cellular factor. The RNA immunoprecipitation experiment confirmed that the FMDV CRE interacts with PCBP2 protein. CRE derived from FMDV infection in pig bound stronger to PCBP2 protein of pig than cattle PCBP2, showing host specific RNA-protein interaction. In addition, PCBP2 interacts with FMDV 3B protein together with CRE. The interaction of PCBP and 3B protein with CRE also showed host-specific manners. III. Conclusions: These data suggest that cellular PCBP2 may serve as a host cellular factor of FMDV to facilitate viral replication through interaction with the viral genome and contribute to determine host susceptibility of FMDV variants. The inter-molecular interaction between cellular PCBP2 and FMDV 3B and CRE provides perspectives for antiviral strategy.