title: Construction and characterization of infectious hepatitis C virus chimera containing structural proteins directly from genotype 1b clinical isolates.
abstract: HCV genotype is a major determinant of clinical outcome, and GT1b HCV infection is the most difficult to treat and also the predominant genotype in East Asia and Europe. We developed 1b/JFH-1 inter-genotypic recombinants containing the structural genes (Core, E1, E2), p7 and the 1stTMD of NS2 directly from GT1b clinical isolates. Through a cloning selection strategy, we obtained 4 functional clones from 3 cases of GT1b patients' sera, which could produce infectious viruses in Huh7.5.1 cells. Sequencing analysis of recovered viruses from serial passage and reverse genetics revealed that adaptive mutations in the GT1b-originated region were enough for the enhancement of infectivity. A monoclonal antibody to E2 and original patient sera could efficiently block 3 of the viruses (26C3mt, 52B6mt and 79L9) while had little effect on 26C6mt viruses. The availability of 1b/JFH-1 chimeric viruses will be important for studies of isolate-specific neutralization and useful in evaluating antiviral therapies.
authors.affiliation: Unit of Viral Hepatitis, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Wanyin
authors.initials: W
authors.lastname: Tao
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiang
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Jin
authors.initials: J
authors.lastname: Zhong
mesh_terms: D001208:Asia; D002460:Cell Line; D005060:Europe; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D015678:Viral Structural Proteins / Q000235:genetics*; D014779:Virus Replication
chemical_list: D015678:Viral Structural Proteins