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Efficient replication of primary or culture hepatitis C virus isolates in human liver slices: A relevant ex vivo model of liver infection
Author(s) -
Lagaye Sylvie,
Shen Hong,
Saunier Bertrand,
Nascimbeni Michelina,
Gaston Jesintha,
Bourdoncle Pierre,
Hannoun Laurent,
Massault PierrePhilippe,
ValletPichard Anaïs,
Mallet Vincent,
Pol Stanislas
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25738
Subject(s) - ex vivo , virology , hepatitis c virus , fulminant hepatitis , biology , viral replication , virus , in vivo , titer , hepatology , hepacivirus , viral life cycle , immunology , medicine , microbiology and biotechnology
The development of human cultured hepatitis C virus (HCV) replication‐permissive hepatocarcinoma cell lines has provided important new virological tools to study the mechanisms of HCV infection; however, this experimental model remains distantly related to physiological and pathological conditions. Here, we report the development of a new ex vivo model using human adult liver slices culture, demonstrating, for the first time, the ability of primary isolates to undergo de novo viral replication with the production of high‐titer infectious virus as well as Japanese fulminant hepatitis type 1, H77/C3, and Con1/C3. This experimental model was employed to demonstrate HCV neutralization or HCV inhibition, in a dose‐dependent manner, either by cluster of differentiation 81 or envelope protein 2–specific antibodies or convalescent serum from a recovered HCV patient or by antiviral drugs. Conclusion : This new ex vivo model represents a powerful tool for studying the viral life cycle and dynamics of virus spread in native tissue and also allows one to evaluate the efficacy of new antiviral drugs. (H EPATOLOGY 2012;56:861–872)