Non-genotype-specific role of the hepatitis C virus 5' untranslated region in virus production and in inhibition by interferon

TY - JOUR

T1 - Non-genotype-specific role of the hepatitis C virus 5' untranslated region in virus production and in inhibition by interferon

AU - Li, Yi-Ping

AU - Ramirez, Santseharay

AU - Gottwein, Judith M

AU - Bukh, Jens

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011/12/20

Y1 - 2011/12/20

N2 - 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-α2b. 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.

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-α2b. 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.

KW - 5' Untranslated Regions

KW - Base Sequence

KW - Cell Line

KW - Genotype

KW - Hepacivirus

KW - Humans

KW - Interferon-alpha

KW - RNA, Viral

KW - Recombinant Proteins

KW - Sequence Analysis, DNA

KW - Viral Core Proteins

KW - Virus Replication

U2 - 10.1016/j.virol.2011.10.002

DO - 10.1016/j.virol.2011.10.002

M3 - Journal article

C2 - 22029937

SN - 1178-122X

VL - 421

SP - 222

EP - 234

JO - Virology: Research and Treatment

JF - Virology: Research and Treatment

IS - 2

ER -