Development of an Infectious Surrogate Hepatitis C Virus Based on a Recombinant Vesicular Stomatitis Virus Expressing Hepatitis C Virus Envelope Glycoproteins and Green Fluorescent Protein

DOI Web Site PubMed 参考文献29件
  • Okuma Kazu
    Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases
  • Fukagawa Koji
    Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases Technology and Product Development Division, Diagnostic Reagent Development, Sysmex Corporation
  • Tateyama Seiji
    Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases Medical Facilities Support Department, Micron Inc.
  • Kohma Takuya
    Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases Technology and Product Development Division, Diagnostic Reagent Development, Sysmex Corporation
  • Mochida Keiko
    Department of Bacterial Pathogenesis and Infection, National Institute of Infectious Diseases
  • Hiyoshi Masateru
    Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases
  • Takahama Youichi
    Technology and Product Development Division, Diagnostic Reagent Development, Sysmex Corporation
  • Hamaguchi Yukio
    Technology and Product Development Division, Diagnostic Reagent Development, Sysmex Corporation
  • Hirose Kunitaka
    Medical Facilities Support Department, Micron Inc.
  • Buonocore Linda
    Department of Pathology, Yale University School of Medicine
  • Rose John K.
    Department of Pathology, Yale University School of Medicine
  • Mizuochi Toshiaki
    Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases
  • Hamaguchi Isao
    Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases

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To develop surrogate viruses for hepatitis C virus (HCV), we previously produced recombinant vesicular stomatitis viruses (rVSVs) lacking glycoprotein G but instead expressing chimeric HCV E1/E2 fused to G. These rVSVs were not infectious in HCV-susceptible hepatoma cells. In this study, to develop an infectious surrogate HCV based on an rVSV (vesicular stomatitis virus [VSV]/HCV), we generated a novel rVSV encoding the native E1/E2 (H77 strain) and green fluorescent protein (GFP) instead of G. Here, we showed that this VSV/HCV efficiently infected human hepatoma cells, including Huh7 human hepatoma cells, expressed GFP in these cells, and propagated, but did not do so in nonsusceptible BHK-21 cells. The infectivity of VSV/HCV, measured as the number of foci of GFP-positive cells, was specifically reduced by the addition of chimpanzee anti-HCV serum, anti-E2 antibody, or anti-CD81 antibody to the cultures. When sera obtained from HCV-infected or uninfected patients were added, infection was selectively inhibited only by the sera of HCV-infected patients. These data together suggest that this infectious GFP-expressing VSV/HCV could be a useful tool for studying the mechanisms of HCV entry into cells and for assessing potential inhibitors of viral entry, including neutralizing antibodies.

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