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

Kazu Okuma; Koji Fukagawa; Seiji Tateyama; Takuya Kohma; Keiko Mochida; Masateru Hiyoshi; Youichi Takahama; Yukio Hamaguchi; Kunitaka Hirose; Linda Buonocore; John K. Rose; Toshiaki Mizuochi; Isao Hamaguchi

doi:10.7883/yoken.JJID.2014.328

Original Article

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

Kazu Okuma, Koji Fukagawa, Seiji Tateyama, Takuya Kohma, Keiko Mochida, Masateru Hiyoshi, Youichi Takahama, Yukio Hamaguchi, Kunitaka Hirose, Linda Buonocore, John K. Rose, Toshiaki Mizuochi, Isao Hamaguchi

Author information

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

Keywords: HCV, VSV, surrogate virus, E1E2, GFP

JOURNAL FREE ACCESS

2015 Volume 68 Issue 3 Pages 203-208

DOI https://doi.org/10.7883/yoken.JJID.2014.328

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Abstract

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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