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.

Advances and Breakthroughs in IRES-Directed Translation and Replication of Picornaviruses

“…A recent study has shown that pycnogenol (a compound of natural chemicals from the bark of a fine European tree) was treated for 72 h in the B10 cell line expressing FMDV IRES, which showed a significant decrease in FMDV IRES activity. Additional results showed that 115 host genes were downregulated using pycnogenol, which suggested that the suppression of FMDV IRES activity could be due to the downregulation of host genes ( 131 ). Studies regarding herbal extracts summarized in this review, compared to type I IRES viruses, the herbal extracts that can potentially restrict IRES-dependent translation are negligible in type II IRES viruses, especially those against FMDV.…”