Journal
VIROLOGY
Volume 314, Issue 1, Pages 16-25Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0042-6822(03)00383-0
Keywords
HCV; three-dimensional radial-flow bioreactor; replication; full-length cDNA; infectious clone; particles; reverse genetics; infection; in vitro culture model; artificial liver
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Lack of efficient culture systems for hepatitis C virus (HCV) has been a major obstacle in HCV research. Human liver cells grown in a three-dimensional radial-flow bioreactor were successfully infected following inoculation with plasma from an HCV carrier. Subsequent detection of increased HCV RNA suggested viral replication. Furthermore, transfection of HCV RNA transcribed from full-length cDNA also resulted in the production and release of HCV virions into supernatant. Infectivity was shown by successful secondary passage to a new culture. Introduction of mutations in RNA helicase and polymerase regions of HCV cDNA abolished virus replication, indicating that reverse genetics of this system is possible. he ability to replicate and detect the extracellular release of HCV might provide clues with regard to the persistent nature of HCV infection. It will also accelerate research into the pathogenicity of HCV, as well as the development of prophylactic agents and new therapy. (C) 2003 Elsevier Inc. All rights reserved.
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