{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:42:36Z","timestamp":1784767356932,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science, and Culture, Japan","award":["20H3164"],"award-info":[{"award-number":["20H3164"]}]},{"name":"Japanese Agency for Medical Research and Development","award":["JP253fa827017"],"award-info":[{"award-number":["JP253fa827017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Host factors play critical roles in viral IRES-mediated translation by modulating the efficiency and specificity of viral protein synthesis. In this study, we used small interfering RNA (siRNA) treatment to silence and plasmid-based expression to overexpress PKD1L3 and USP31. Silencing PKD1L3 and USP31 suppressed IRES activity in FMDV and CSFV RNAs, whereas the overexpression of PKD1L3 did not have a significant effect, and USP31 overexpression resulted in only a modest increase in CSFV-IRES activity. Silencing PKD1L3 significantly reduced EMCV-IRES activity but had no significant effect on HCV- or DENV-IRES activity, and silencing USP31 had no significant effect on the activities of these three IRESs. Notably, the combined overexpression of PKD1L3 and USP31 significantly suppressed HCV-IRES activity, suggesting potential context-dependent interactions. These findings indicated that PKD1L3 and USP31 contribute more prominently to CSFV-, FMDV-, and EMCV-IRES-mediated translation than to HCV- or DENV-IRES-driven translation. Collectively, our results provide new insights into the host factors involved in IRES-mediated viral translation, establish a foundation for future in vivo studies to elucidate the specific roles of PKD1L3 and USP31 during viral infection, and indicate potential strategies for mitigating these viruses.<\/jats:p>","DOI":"10.3390\/vetsci12121128","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T08:26:57Z","timestamp":1764318417000},"page":"1128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of the Regulatory Effects of Host Factors on Viral Internal Ribosomal Entry Sites"],"prefix":"10.3390","volume":"12","author":[{"given":"Rupaly","family":"Akhter","sequence":"first","affiliation":[{"name":"Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"},{"name":"Department of Pharmacology & Toxicology, Faculty of Animal Science and Veterinary Medicine, Sher-e-Bangla Agricultural University, Sher-e-Bangla Nagar, Dhaka 1207, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazi Anowar","family":"Hossain","sequence":"additional","affiliation":[{"name":"Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bouchra","family":"Kitab","sequence":"additional","affiliation":[{"name":"Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4806-9843","authenticated-orcid":false,"given":"Mohammad Enamul Hoque","family":"Kayesh","sequence":"additional","affiliation":[{"name":"Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"},{"name":"Department of Microbiology and Public Health, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal 8210, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-2018","authenticated-orcid":false,"given":"Kyoko","family":"Tsukiyama-Kohara","sequence":"additional","affiliation":[{"name":"Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tibs.2008.04.007","article-title":"Viral IRES RNA structures and ribosome interactions","volume":"33","author":"Kieft","year":"2008","journal-title":"Trends Biochem. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.coviro.2015.04.008","article-title":"Structural insights into viral IRES-dependent translation mechanisms","volume":"12","author":"Lozano","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1128\/CMR.17.2.465-493.2004","article-title":"Foot-and-mouth disease","volume":"17","author":"Grubman","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1128\/jvi.64.11.5389-5395.1990","article-title":"A region of the 5\u2032 noncoding region of foot-and-mouth disease virus RNA directs efficient internal initiation of protein synthesis within cells: Involvement with the role of L protease in translational control","volume":"64","author":"Belsham","year":"1990","journal-title":"J. Virol."},{"key":"ref_5","first-page":"985","article-title":"Internal initiation of translation in eukaryotes: The picornavirus paradigm and beyond","volume":"1","author":"Jackson","year":"1995","journal-title":"RNA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1128\/jvi.66.3.1476-1483.1992","article-title":"Internal ribosome entry site within hepatitis C virus RNA","volume":"66","author":"Iizuka","year":"1992","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, Y., Zhang, L., Wang, L., Li, J., Zhao, Y., Liu, F., and Wang, Q. (2024). Structure and function of type IV IRES in picornaviruses: A systematic review. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1415698"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Arhab, Y., Bulakhov, A.G., Pestova, T.V., and Hellen, C.U.T. (2020). Dissemination of Internal Ribosomal Entry Sites (IRES) Between Viruses by Horizontal Gene Transfer. Viruses, 12.","DOI":"10.3390\/v12060612"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nrmicro2655","article-title":"Viral subversion of the host protein synthesis machinery","volume":"9","author":"Walsh","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41579-018-0117-x","article-title":"Viral RNA structure-based strategies to manipulate translation","volume":"17","author":"Jaafar","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev-virology-100114-055014","article-title":"A Cap-to-Tail Guide to mRNA Translation Strategies in Virus-Infected Cells","volume":"3","author":"Jan","year":"2016","journal-title":"Annu. Rev. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pacheco, A., and Martinez-Salas, E. (2010). Insights into the biology of IRES elements through riboproteomic approaches. J. Biomed. Biotechnol., 2010.","DOI":"10.1155\/2010\/458927"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4782","DOI":"10.1002\/pmic.200800338","article-title":"Riboproteomic analysis of polypeptides interacting with the internal ribosome-entry site element of foot-and-mouth disease viral RNA","volume":"8","author":"Pacheco","year":"2008","journal-title":"Proteomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.tibs.2017.06.002","article-title":"Ribosomal Chamber Music: Toward an Understanding of IRES Mechanisms","volume":"42","author":"Yamamoto","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1261\/rna.469707","article-title":"Differential factor requirement to assemble translation initiation complexes at the alternative start codons of foot-and-mouth disease virus RNA","volume":"13","author":"Andreev","year":"2007","journal-title":"RNA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.tim.2017.01.010","article-title":"Regulation Mechanisms of Viral IRES-Driven Translation","volume":"25","author":"Lee","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2506281122","DOI":"10.1073\/pnas.2506281122","article-title":"ITAF(45) is a pervasive trans-acting factor for picornavirus Type II IRES elements","volume":"122","author":"Bellucci","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ide, Y., Kitab, B., Ito, N., Okamoto, R., Tamura, Y., Matsui, T., Sakoda, Y., and Tsukiyama-Kohara, K. (2022). Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-10437-z"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"199570","DOI":"10.1016\/j.virusres.2025.199570","article-title":"Common host factors for internal ribosomal entry site-mediated translation of viral genomic RNA: An investigation in foot-and-mouth disease and classical swine fever viruses","volume":"355","author":"Akhter","year":"2025","journal-title":"Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1007\/s00018-016-2409-5","article-title":"A researcher\u2019s guide to the galaxy of IRESs","volume":"74","author":"Terenin","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.antiviral.2014.10.017","article-title":"Inhibitory effects of Pycnogenol(R) on hepatitis C virus replication","volume":"113","author":"Ezzikouri","year":"2015","journal-title":"Antiviral Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199244","DOI":"10.1016\/j.virusres.2023.199244","article-title":"Suppression of dengue virus replication by the French maritime pine extract Pycnogenol(R)","volume":"339","author":"Hossain","year":"2023","journal-title":"Virus Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1093\/nar\/gkg199","article-title":"A promoter activity is present in the DNA sequence corresponding to the hepatitis C virus 5\u2032 UTR","volume":"31","author":"Dumas","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1007\/s11262-019-01696-6","article-title":"Silencing of the foot-and-mouth disease virus internal ribosomal entry site by targeting relatively conserved region among serotypes","volume":"55","author":"Matsui","year":"2019","journal-title":"Virus Genes"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kanda, T., Ozawa, M., and Tsukiyama-Kohara, K. (2016). IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals. BMC Vet. Res., 12.","DOI":"10.1186\/s12917-016-0694-8"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1099\/vir.0.040386-0","article-title":"Promotion of viral internal ribosomal entry site-mediated translation under amino acid starvation","volume":"93","author":"Licursi","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1128\/jvi.63.4.1651-1660.1989","article-title":"Initiation of protein synthesis by internal entry of ribosomes into the 5\u2032 nontranslated region of encephalomyocarditis virus RNA in vivo","volume":"63","author":"Jang","year":"1989","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e01998-20","DOI":"10.1128\/JVI.01998-20","article-title":"The internal ribosome entry site of the Dengue virus mRNA is active when cap-dependent translation initiation is inhibited","volume":"95","author":"Angulo","year":"2021","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.celrep.2015.09.041","article-title":"Influx-Operated Ca(2+) Entry via PKD2-L1 and PKD1-L3 Channels Facilitates Sensory Responses to Polymodal Transient Stimuli","volume":"13","author":"Hu","year":"2015","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12569","DOI":"10.1073\/pnas.0602702103","article-title":"Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor","volume":"103","author":"Ishimaru","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e0001523","DOI":"10.1128\/jvi.00015-23","article-title":"Calcium Influx Regulates the Replication of Several Negative-Strand RNA Viruses Including Severe Fever with Thrombocytopenia Syndrome Virus","volume":"97","author":"Urata","year":"2023","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1186\/s12964-025-02357-y","article-title":"The crucial role of intercellular calcium wave propagation triggered by influenza A virus in promoting infection","volume":"23","author":"Kozawa","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Qu, Y., Sun, Y., Yang, Z., and Ding, C. (2022). Calcium Ions Signaling: Targets for Attack and Utilization by Viruses. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.889374"},{"key":"ref_34","first-page":"189","article-title":"Targeting internal ribosome entry site (IRES)-mediated translation to block hepatitis C and other RNA viruses","volume":"234","author":"Dasgupta","year":"2004","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nrd937","article-title":"Hepatitis C therapeutics: Current status and emerging strategies","volume":"1","author":"Tan","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.virusres.2011.10.003","article-title":"The interaction between human initiation factor eIF3 subunit c and heat-shock protein 90: A necessary factor for translation mediated by the hepatitis C virus internal ribosome entry site","volume":"163","author":"Ujino","year":"2012","journal-title":"Virus Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"gkaf445","DOI":"10.1093\/nar\/gkaf445","article-title":"Comprehensive mutational analysis of the sequence-function relationship within a viral internal ribosome entry site","volume":"53","author":"Grunseich","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9294","DOI":"10.1093\/nar\/gkad569","article-title":"The structure and mechanism of action of a distinct class of dicistrovirus intergenic region IRESs","volume":"51","author":"Abaeva","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Song, K., and Li, S. (2021). The Role of Ubiquitination in NF-kappaB Signaling during Virus Infection. Viruses, 13.","DOI":"10.3390\/v13020145"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cellsig.2005.03.017","article-title":"Human ubiquitin specific protease 31 is a deubiquitinating enzyme implicated in activation of nuclear factor-kappaB","volume":"18","author":"Tzimas","year":"2006","journal-title":"Cell Signal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1046\/j.1471-4159.2003.02024.x","article-title":"A novel ubiquitin-specific protease, synUSP, is localized at the post-synaptic density and post-synaptic lipid raft","volume":"87","author":"Tian","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1158\/0008-5472.CAN-17-4052","article-title":"YAP1-Mediated Suppression of USP31 Enhances NFkappaB Activity to Promote Sarcomagenesis","volume":"78","author":"Ye","year":"2018","journal-title":"Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/abbs\/gmab080","article-title":"USP31 acetylation at Lys1264 is essential for its activity and cervical cancer cell growth","volume":"53","author":"Hou","year":"2021","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"426","DOI":"10.17305\/bjbms.2022.8440","article-title":"Systemic analysis of the expression and prognostic significance of USP31 in endometrial cancer","volume":"23","author":"Huang","year":"2023","journal-title":"Biomol. Biomed."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/12\/12\/1128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T09:00:12Z","timestamp":1764320412000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/12\/12\/1128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["vetsci12121128"],"URL":"https:\/\/doi.org\/10.3390\/vetsci12121128","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]}}}