title: Modification of the internal ribosome entry site element impairs the growth of foot-and-mouth disease virus in porcine-derived cells.
abstract: The 5' untranslated region (5'UTR) of foot-and-mouth disease virus (FMDV) contains an internal ribosome entry site (IRES) that facilitates translation initiation of the viral ORF in a 5' (m7GpppN) cap-independent manner. IRES elements are responsible for the virulence phenotypes of several enteroviruses. Here, we constructed a chimeric virus in which the IRES of FMDV was completely replaced with that of bovine rhinitis B virus (BRBV) in an infectious clone of serotype O FMDV. The resulting IRES-replaced virus, FMDV(BRBV), replicated as efficiently as WT FMDV in hamster-derived BHK-21 cells, but was restricted for growth in porcine-derived IBRS-2, PK-15 and SK-6 cells, which are susceptible to WT FMDV. To identify the genetic determinants of FMDV underlying this altered cell tropism, a series of IRES-chimeric viruses were constructed in which each domain of the FMDV IRES was replaced with its counterpart from the BRBV IRES. The replication kinetics of these chimeric viruses in different cell lines revealed that the growth restriction phenotype in porcine-derived cells was produced after the replacement of domain 3 or 4 in the FMDV IRES. Furthermore, the change in FMDV cell tropism due to IRES replacement in porcine-derived cells was mainly attributed to a decline in cell-specific IRES translation initiation efficiency. These findings demonstrate that IRES domains 3 and 4 of FMDV are novel cell-specific cis-elements for viral replication in vitro and suggest that IRES-mediated translation determines the species specificity of FMDV infection in vivo.
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina.
authors.forename: Decheng
authors.initials: D
authors.lastname: Yang
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina.
authors.forename: Rongyuan
authors.initials: R
authors.lastname: Gao
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina.
authors.forename: Te
authors.initials: T
authors.lastname: Liang
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina.
authors.forename: Guohui
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002678:Chimera / Q000235:genetics; D003412:Cricetulus; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000254:growth & development; D015967:Gene Expression Regulation, Viral; D007242:Herpesvirus 1, Bovine / Q000235:genetics*; D058507:Host Specificity; D000067556:Internal Ribosome Entry Sites; D007668:Kidney / Q000473:pathology / Q000821:virology; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016865:Reassortant Viruses / Q000235:genetics* / Q000254:growth & development; D012093:Replicon; D012270:Ribosomes; D013552:Swine; D056189:Viral Tropism; D014779:Virus Replication
chemical_list: D000067556:Internal Ribosome Entry Sites; D012367:RNA, Viral