Construction and characterization of infectious hepatitis C virus chimera containing structural proteins directly from genotype 1b clinical isolates.

Jie Lu, Wanyin Tao, Rui Li, Yu Xiang, Nan Zhang, Xiaogang Xiang, Qing Xie, Jin Zhong

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.

Virology 2013 Aug 15

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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. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Jie Lu, Wanyin Tao, Rui Li, Yu Xiang, Nan Zhang, Xiaogang Xiang, Qing Xie, Jin Zhong. Construction and characterization of infectious hepatitis C virus chimera containing structural proteins directly from genotype 1b clinical isolates. Virology. 2013 Aug 15;443(1):80-8