title: IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals.
abstract: BACKGROUND
  Foot-and-mouth disease virus (FMDV) possess a positive sense, single stranded RNA genome. Internal ribosomal entry site (IRES) element exists within its 5' untranslated region (5'UTR) of the viral RNA. Translation of the viral RNA is initiated by internal entry of the 40S ribosome within the IRES element. This process is facilitated by cellular factors known as IRES trans-acting factors (ITAFs). Foot-and-mouth disease (FMD) is host-restricted disease for cloven-hoofed animals such as cattle and pigs, but the factors determining the host range have not been identified yet. Although, ITAFs are known to promote IRES-mediated translation, these findings were confirmed only in cells derived from FMDV-insusceptible animals so far. We evaluated and compared the IRES-mediated translation activities among cell lines derived from four different animal species using bicistronic luciferase reporter plasmid, which possesses an FMDV-IRES element between Renilla and Firefly luciferase genes. Furthermore, we analyzed the effect of the cellular factors on IRES-mediated translation by silencing the cellular factors using siRNA in both FMDV-susceptible and -insusceptible animal cells.
  
  
  RESULTS
  Our data indicated that IRES-mediated translational activity was not linked to FMDV host range. ITAF45 promoted IRES-mediated translation in all cell lines, and the effects of poly-pyrimidine tract binding protein (PTB) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were observed only in FMDV-susceptible cells. Thus, PTB and 4E-BP1 may influence the host range of FMDV.
  
  
  CONCLUSIONS
  IRES-mediated translation activity of FMDV was not predictive of its host range. ITAF45 promoted IRES-mediated translation in all cells, and the effects of PTB and 4E-BP1 were observed only in FMDV-susceptible cells.
authors.affiliation: Department of Animal Hygiene, Joint Facility of Veterinary Medicine, Kagoshima University, Kagoshima, Kagoshima, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Animal Hygiene, Joint Facility of Veterinary Medicine, Kagoshima University, Kagoshima, Kagoshima, Japan.|Transboundary Animal Disease Center, Joint Facility of Veterinary Medicine, Kagoshima University, Kagoshima, Kagoshima, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Department of Animal Hygiene, Joint Facility of Veterinary Medicine, Kagoshima University, Kagoshima, Kagoshima, Japan. kkohara@vet.kagoshima-u.ac.jp.|Transboundary Animal Disease Center, Joint Facility of Veterinary Medicine, Kagoshima University, Kagoshima, Kagoshima, Japan. kkohara@vet.kagoshima-u.ac.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsukiyama-Kohara
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D004198:Disease Susceptibility; D004285:Dogs; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D058507:Host Specificity / Q000502:physiology*; D058605:Host-Derived Cellular Factors / Q000378:metabolism; D006801:Humans; D000067556:Internal Ribosome Entry Sites / Q000235:genetics / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013552:Swine
chemical_list: D058605:Host-Derived Cellular Factors; D000067556:Internal Ribosome Entry Sites; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D038941:Polypyrimidine Tract-Binding Protein
keywords: 4E-BP1; FMDV; IRES; ITAF; ITAF45; PTB; Translation