PMID- 24026670 OWN - NLM STAT- MEDLINE DCOM- 20140121 LR - 20211021 IS - 1465-2099 (Electronic) IS - 0022-1317 (Print) IS - 0022-1317 (Linking) VI - 94 IP - Pt 12 DP - 2013 Dec TI - The non-primate hepacivirus 5' untranslated region possesses internal ribosomal entry site activity. PG - 2657-2663 LID - 10.1099/vir.0.055764-0 [doi] AB - 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. FAU - Stewart, Hazel AU - Stewart H AD - School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. FAU - Walter, Cheryl AU - Walter C AD - School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. FAU - Jones, Dale AU - Jones D AD - School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. FAU - Lyons, Sinead AU - Lyons S AD - Infection and Immunity Division, The Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK. FAU - Simmonds, Peter AU - Simmonds P AD - Infection and Immunity Division, The Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK. FAU - Harris, Mark AU - Harris M AD - School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. LA - eng GR - 095831/Wellcome Trust/United Kingdom GR - 096670/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130911 PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (5' Untranslated Regions) RN - 0 (RNA, Viral) SB - IM MH - 5' Untranslated Regions/*genetics/physiology MH - Animals MH - Cell Line MH - HEK293 Cells MH - Hepacivirus/*genetics/metabolism/physiology MH - Humans MH - Nucleic Acid Conformation MH - *Peptide Chain Initiation, Translational MH - Primates/genetics/metabolism MH - RNA, Viral/genetics/metabolism MH - Replicon/genetics/physiology MH - Ribosomes/*metabolism MH - Virus Replication/genetics PMC - PMC3836496 EDAT- 2013/09/13 06:00 MHDA- 2014/01/22 06:00 PMCR- 2013/12/01 CRDT- 2013/09/13 06:00 PHST- 2013/09/13 06:00 [entrez] PHST- 2013/09/13 06:00 [pubmed] PHST- 2014/01/22 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - 055764 [pii] AID - 10.1099/vir.0.055764-0 [doi] PST - ppublish SO - J Gen Virol. 2013 Dec;94(Pt 12):2657-2663. doi: 10.1099/vir.0.055764-0. Epub 2013 Sep 11.