Comprehensive screening of host proteins that suppress replication of HCV replicon

点击翻译按钮获取中文摘要

We have conducted studies of comprehensive screening of host proteins that suppress hepatitis C virus (HCV) replication using HCV subgenomic replication models and cell culture models.(1) High throughput screening of a library of 2,500 bioactive drugs, peptides, and compounds : we found 52 compounds that suppress or augment HCV replication (Gastroenterology 2006).(2) Establishment of antiviral therapies that target molecular chaperone and cyclophillin : we have reported that cyclosporine A suppress HCV replication through blockade of action of cyclophiline A, B and C. In this study, we next screened host proteins that interact with cyclophillins by bacterial two-hybrid system assay, and identified several proteins including G-protein coupled protein. We are now conducting studies to investigate functions of the proteins.(3) Screening of interferon-stimulated genes that suppress HCV replication : type-I interferon is a key molecule to mediate host virus defense functions. We have newly identified that three IGSs, GBP1, IFI27 and IFI6-16, show suppressive effects on HCV replication. Through immune precipitation assay, we have found that GBP-1 specifically binds HCV-NS5B RNA polymerase.With the above result we are now further conduct screening of antiviral compounds. These results may contribute to establish novel antiviral therapeutics.