Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses

• Published in: Scientific reports Vol. 12; no. 1; pp. 6709 - 11
• Main Authors: Ide, Yutaro, Kitab, Bouchra, Ito, Nobumasa, Okamoto, Riai, Tamura, Yui, Matsui, Takafumi, Sakoda, Yoshihiro, Tsukiyama-Kohara, Kyoko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.04.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 5' Untranslated regions; 631/326; 631/337; Animals; Antiviral activity; Antiviral drugs; Cell lines; Classical Swine Fever; Classical Swine Fever Virus - genetics; Classical Swine Fever Virus - metabolism; Fever; Foot & mouth disease; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus - genetics; Genomes; Hog cholera; Humanities and Social Sciences; Internal Ribosome Entry Sites; Kidney diseases; multidisciplinary; Peptidase; Polycystic kidney; Pycnogenol; Science; Science (multidisciplinary); siRNA; Swine; Ubiquitin; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-10437-z

Foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV) possess positive-sense single-stranded RNA genomes and an internal ribosomal entry site (IRES) element within their 5′-untranslated regions. To investigate the common host factors associated with these IRESs, we established cell lines expressing a bicistronic luciferase reporter plasmid containing an FMDV-IRES or CSFV-IRES element between the Renilla and firefly luciferase genes. First, we treated FMDV-IRES cells with the French maritime pine extract, Pycnogenol (PYC), and examined its suppressive effect on FMDV-IRES activity, as PYC has been reported to have antiviral properties. Next, we performed microarray analysis to identify the host factors that modified their expression upon treatment with PYC, and confirmed their function using specific siRNAs. We found that polycystic kidney disease 1-like 3 (PKD1L3) and ubiquitin-specific peptidase 31 (USP31) were associated with FMDV-IRES activity. Moreover, silencing of these factors significantly suppressed CSFV-IRES activity. Thus, PKD1L3 and USP31 are host factors associated with the functions of FMDV- and CSFV-IRES elements.