Common Host Factors Involved in the Function of the Foot-and-mouth Disease Virus and Classical Swine Fever Virus Internal Ribosomal Entry Sites

Abstract Foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV) both possess positive strand RNA genomes and an internal ribosomal entry site (IRES) element within their 5¢-untranslated regions. To identify common host factors involved with the activity of these IRESes, we utilized cell lines expressing a bicistronic luciferase reporter plasmid, which contained an FMDV-IRES or CSFV-IRES element between the Renilla and firefly luciferase genes. First, we treated FMDV-IRES cells with French maritime pine extract, Pycnogenol® (PYC), and evaluated its suppressive effect on FMDV-IRES activity, as anti-viral effect of PYC was reported so far. We next performed microarray analysis to identify host factors affected by PYC, and confirmed host-factor-IRES interaction by applying host factor-specific siRNAs. We found that polycystic kidney disease 1-like 3 (PKD1L3) and ubiquitin specific peptidase 31 (USP31) are involved in FMDV-IRES activity. Moreover, silencing of these factors also significantly suppressed CSFV-IRES activity. Accordingly, we suggest that PKD1L3 and USP31 are host factors that are involved in the function of the FMDV and CSFV-IRES elements.