PMID- 26795299 OWN - NLM STAT- MEDLINE DCOM- 20160823 LR - 20191209 IS - 1465-2099 (Electronic) IS - 0022-1317 (Print) IS - 0022-1317 (Linking) VI - 97 IP - 4 DP - 2016 Apr TI - Modification of the internal ribosome entry site element impairs the growth of foot-and-mouth disease virus in porcine-derived cells. PG - 901-911 LID - 10.1099/jgv.0.000406 [doi] AB - 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. FAU - Sun, Chao AU - Sun C AD - Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina. FAU - Yang, Decheng AU - Yang D AD - Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina. FAU - Gao, Rongyuan AU - Gao R AD - Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina. FAU - Liang, Te AU - Liang T AD - Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina. FAU - Wang, Haiwei AU - Wang H AD - Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina. FAU - Zhou, Guohui AU - Zhou G AD - Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina. FAU - Yu, Li AU - Yu L AD - Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PRChina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160120 PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (Internal Ribosome Entry Sites) RN - 0 (RNA, Viral) SB - IM MH - Animals MH - Base Sequence MH - Cell Line MH - Chimera/genetics MH - Cricetulus MH - Epithelial Cells/pathology/virology MH - Foot-and-Mouth Disease Virus/*genetics/growth & development MH - *Gene Expression Regulation, Viral MH - Herpesvirus 1, Bovine/*genetics MH - Host Specificity MH - *Internal Ribosome Entry Sites MH - Kidney/pathology/virology MH - Molecular Sequence Data MH - Peptide Chain Initiation, Translational MH - RNA, Viral/genetics/metabolism MH - Reassortant Viruses/*genetics/growth & development MH - Replicon MH - Ribosomes MH - Swine MH - *Viral Tropism MH - Virus Replication PMC - PMC4854365 EDAT- 2016/01/23 06:00 MHDA- 2016/08/24 06:00 PMCR- 2017/04/01 CRDT- 2016/01/23 06:00 PHST- 2016/01/23 06:00 [entrez] PHST- 2016/01/23 06:00 [pubmed] PHST- 2016/08/24 06:00 [medline] PHST- 2017/04/01 00:00 [pmc-release] AID - 000406 [pii] AID - 10.1099/jgv.0.000406 [doi] PST - ppublish SO - J Gen Virol. 2016 Apr;97(4):901-911. doi: 10.1099/jgv.0.000406. Epub 2016 Jan 20.