title: Persistent replication of a hepatitis C virus genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B in a New World monkey.
abstract: The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (<200 copies/mL), the viral RNA loads in plasma were detectable intermittently during the observation period. Of note, the chimeric RNA was found in the pellet fraction obtained by ultracentrifugation of the plasma at 73 weeks, indicating production of the chimeric virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome.
authors.affiliation: Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506.
authors.forename: Saori
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Advanced Life Science Institute, 2-10-23 Maruyamadai, Wako, Saitama 351-0112.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Mori
authors.affiliation: Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Higashino
authors.affiliation: Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
authors.affiliation: Advanced Life Science Institute, 2-10-23 Maruyamadai, Wako, Saitama 351-0112.
authors.forename: Noboru
authors.initials: N
authors.lastname: Maki
authors.affiliation: Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506.|Laboratory of Evolutional Virology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Akari
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002678:Chimera / Q000235:genetics / Q000821:virology; D004195:Disease Models, Animal; D018178:Flaviviridae Infections / Q000821:virology; D029406:GB virus B / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006524:Hepatitis, Viral, Animal / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000821:virology*; D051078:Platyrrhini / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics; D014761:Viral Hepatitis Vaccines / Q000276:immunology; D017361:Viral Nonstructural Proteins; D014779:Virus Replication / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins
keywords: GB virus B; animal model; hepatitis C virus; persistent replication