PMID- 22029937 OWN - NLM STAT- MEDLINE DCOM- 20120117 LR - 20181201 IS - 1096-0341 (Electronic) IS - 0042-6822 (Linking) VI - 421 IP - 2 DP - 2011 Dec 20 TI - Non-genotype-specific role of the hepatitis C virus 5' untranslated region in virus production and in inhibition by interferon. PG - 222-34 LID - 10.1016/j.virol.2011.10.002 [doi] AB - The 5' untranslated region (5'UTR) of hepatitis C virus (HCV) is structured into four domains (I-IV) with numerous genotype-specific nucleotides. It is unknown whether the polymorphisms confer genotype-specific functions to the 5'UTR. Using viable JFH1-based Core-NS2 recombinants, we developed and characterized HCV genotypes 1-7 recombinants with highly diverse 5'UTRs (genotypes 1a and 3a), 2a recombinants (J6/JFH1) with 5'UTR of genotypes 1-6 or with heterotypic chimeric (1a/3a and 3a/1a) 5'UTR domains I, II or III, and 1a recombinants with 5'UTR domain I of genotypes 1-6. All were fully functional in Huh7.5 cells; therefore, the 5'UTR apparently functions in a non-genotype-specific manner in HCV production in vitro. However, adenine at the 5'-terminus was required. We demonstrated that J6/JFH1 with 5'UTR of genotypes 1-6 responded similarly to interferon-alpha2b. This study provides novel insight into the role of the 5'UTR in the HCV life cycle and facilitates HCV basic research and testing of 5'UTR-targeting antivirals. CI - Copyright A(c) 2011 Elsevier Inc. All rights reserved. FAU - Li, Yi-Ping AU - Li YP AD - Copenhagen Hepatitis C Program, Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark. FAU - Ramirez, Santseharay AU - Ramirez S FAU - Gottwein, Judith M AU - Gottwein JM FAU - Bukh, Jens AU - Bukh J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111024 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (5' Untranslated Regions) RN - 0 (Interferon alpha-2) RN - 0 (Interferon-alpha) RN - 0 (RNA, Viral) RN - 0 (Recombinant Proteins) RN - 0 (Viral Core Proteins) SB - IM MH - *5' Untranslated Regions MH - Base Sequence MH - Cell Line MH - Genotype MH - Hepacivirus/drug effects/*genetics/*physiology MH - Humans MH - Interferon alpha-2 MH - Interferon-alpha/*pharmacology MH - RNA, Viral/genetics MH - Recombinant Proteins/pharmacology MH - Sequence Analysis, DNA MH - Viral Core Proteins/genetics MH - Virus Replication/*drug effects/*genetics EDAT- 2011/10/28 06:00 MHDA- 2012/01/18 06:00 CRDT- 2011/10/28 06:00 PHST- 2011/05/27 00:00 [received] PHST- 2011/06/15 00:00 [revised] PHST- 2011/10/03 00:00 [accepted] PHST- 2011/10/28 06:00 [entrez] PHST- 2011/10/28 06:00 [pubmed] PHST- 2012/01/18 06:00 [medline] AID - S0042-6822(11)00470-3 [pii] AID - 10.1016/j.virol.2011.10.002 [doi] PST - ppublish SO - Virology. 2011 Dec 20;421(2):222-34. doi: 10.1016/j.virol.2011.10.002. Epub 2011 Oct 24.