3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV.
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 (PPARalpha) signaling. Furthermore, using PPARalpha agonists and antagonists, we also analyzed the effect of PPARalpha 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.
Aly
Hussein Hassan
HH
Laboratory of Human Tumor Viruses, The Institute for Virus Research, Department of Viral Oncology, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507, Japan.
Shimotohno
Kunitada
K
Hijikata
Makoto
M
D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D047493:PPAR alpha; D007372:Interferons