title: The non-primate hepacivirus 5' untranslated region possesses internal ribosomal entry site activity.
abstract: The 5' untranslated region (5'UTR) of the recently described non-primate hepacivirus (NPHV) contains a region with sequence homology to the internal ribosomal entry site (IRES) of hepatitis C virus (HCV) and GB virus B (GBV-B). Here, we demonstrated internal translation initiation by the NPHV 5'UTR in a bicistronic vector. An RNA stem-loop upstream of the NPHV IRES was structurally distinct from corresponding regions in HCV and GBV-B, and was not required for IRES function. Insertion of the NPHV stem-loop into the corresponding region of the HCV 5'UTR within the HCV subgenomic replicon significantly impaired RNA replication, indicating that long-range interactions between the 5'UTR and cis-acting downstream elements within the NPHV genome are not interchangeable with those of HCV. Despite similarities in IRES structure and function between hepaciviruses, replication elements in the NPHV 5'UTR appear functionally distinct from those of HCV.
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Hazel
authors.initials: H
authors.lastname: Stewart
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Walter
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Dale
authors.initials: D
authors.lastname: Jones
authors.affiliation: Infection and Immunity Division, The Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK.
authors.forename: Sinead
authors.initials: S
authors.lastname: Lyons
authors.affiliation: Infection and Immunity Division, The Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Simmonds
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Harris
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics* / Q000502:physiology; D000818:Animals; D002460:Cell Line; D057809:HEK293 Cells; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D011323:Primates / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012093:Replicon / Q000235:genetics / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D012367:RNA, Viral
references.citation: PLoS One. 2009;4(2):e4419
references.pmid: 19204793
references.citation: RNA. 1996 Oct;2(10):955-68
references.pmid: 8849773
references.citation: mBio. 2013 Apr 09;4(2):e00216-13
references.pmid: 23572554
references.citation: Science. 2005 Sep 2;309(5740):1577-81
references.pmid: 16141076
references.citation: J Virol. 2003 Mar;77(5):3312-8
references.pmid: 12584356
references.citation: J Exp Med. 1967 Apr 1;125(4):673-88
references.pmid: 4960092
references.citation: J Gen Virol. 1977 Jul;36(1):59-74
references.pmid: 886304
references.citation: FEBS Lett. 1995 May 29;365(2-3):115-9
references.pmid: 7781762
references.citation: Lancet Infect Dis. 2005 Sep;5(9):558-67
references.pmid: 16122679
references.citation: Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3401-5
references.pmid: 7724574
references.citation: J Gen Virol. 2012 May;93(Pt 5):951-962
references.pmid: 22302880
references.citation: Emerg Infect Dis. 2012 Dec;18(12):1976-82
references.pmid: 23171728
references.citation: Proc Natl Acad Sci U S A. 2013 May 14;110(20):8194-9
references.pmid: 23610427
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1571-2
references.pmid: 23324744
references.citation: J Virol. 2012 Jun;86(11):6171-8
references.pmid: 22491452
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11608-13
references.pmid: 21610165
references.citation: J Virol. 1992 Mar;66(3):1476-83
references.pmid: 1310759
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):E1407-15
references.pmid: 23509292
references.citation: J Gen Virol. 1999 Sep;80 ( Pt 9):2337-2341
references.pmid: 10501485
references.citation: Cancer Res. 1982 Sep;42(9):3858-63
references.pmid: 6286115
references.citation: Proc Soc Exp Biol Med. 1966 Jul;122(3):931-5
references.pmid: 5918973
references.citation: Virology. 1996 Aug 1;222(1):31-42
references.pmid: 8806485
references.citation: J Virol. 2000 Jan;74(2):773-83
references.pmid: 10623739
references.citation: Nucleic Acids Res. 2012 Dec;40(22):11697-713
references.pmid: 23066110