3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV
- Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, Department of Viral Oncology, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan)
- Center for Human Metabolomic Systems Biology, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan)
Due to the high polymorphism of natural hepatitis C virus (HCV) variants, existing recombinant HCV replication models have failed to be effective in developing effective anti-HCV agents. In the current study, we describe an in vitro system that supports the infection and replication of natural HCV from patient blood using an immortalized primary human hepatocyte cell line cultured in a three-dimensional (3D) culture system. Comparison of the gene expression profile of cells cultured in the 3D system to those cultured in the existing 2D system demonstrated an up-regulation of several genes activated by peroxisome proliferator-activated receptor alpha (PPAR{alpha}) signaling. Furthermore, using PPAR{alpha} agonists and antagonists, we also analyzed the effect of PPAR{alpha} signaling on the modulation of HCV replication using this system. The 3D in vitro system described in this study provides significant insight into the search for novel anti-HCV strategies that are specific to various strains of HCV.
- OSTI ID:
- 21255858
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 379, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.12.054; PII: S0006-291X(08)02435-2; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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