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Live-attenuated vaccines are considered the most effective strategy for prevention, control, and eradication of infectious diseases due to their capacity to induce potent and long-lasting protective immunity. However, efforts to develop FMD virus (FMDV) live-attenuated vaccines have achieved only limited success. Here, by structure-function study of the FMDV internal ribosome entry site (IRES), we find that the C351 mutation of the IRES confers FMDV with an ideal temperature-sensitive attenuation phenotype by decreasing its interaction with cellular pyrimidine tract-binding protein (PTB) to cause IRES-mediated temperature-dependent translation defects. The temperature-sensitive attenuated strains generated by manipulation of the IRES address the challenges of FMDV attenuation differences among various livestock species and immunogenicity maintenance encountered previously, and this strategy can be applied to other viruses with an IRES to rationally design and develop live-attenuated vaccines.<\/jats:p>","DOI":"10.1128\/jvi.00990-20","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T13:57:17Z","timestamp":1591106237000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["A Temperature-Dependent Translation Defect Caused by Internal Ribosome Entry Site Mutation Attenuates Foot-and-Mouth Disease Virus: Implications for Rational Vaccine Design"],"prefix":"10.1128","volume":"94","author":[{"given":"Decheng","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5151-2781","authenticated-orcid":false,"given":"Wenming","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.17.2.465-493.2004"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.08.039"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2016.12.018"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1590\/s0034-89101988000500001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.319.5870.1606"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.036988-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir065"},{"key":"e_1_3_2_9_2","first-page":"73","article-title":"Large-scale cultivation of animal cells in roller bottles for production of decigram amounts of pure foot-and-mouth disease virus","volume":"29","author":"Bachrach HL","year":"1968","unstructured":"Bachrach HL. 1968. 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