| セッション情報 |
特別講演9
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| タイトル |
SL-9：The molecular anatomy of HCV infection：Mapping by functional genomics and chemical biology
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| 演者 |
Liang T. Jake（National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA） |
| 共同演者 |
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| 抄録 |
Hepatitis C virus（HCV）infection is a major cause of end-stage liver disease and a leading indication for liver transplantation. Current therapy is improving but is not yet optimal. HCV depends heavily on host factors not only to establish productive infection but also to trigger unique pathological processes. Each of these host dependencies is a potential therapeutic target. To systematically identify host factors required by HCV, we completed a genome-wide small interfering RNA（siRNA）screen using an infectious HCV cell culture system. In this screen, we demonstrated that hepatitis C virus（HCV）exploits an extensive network of host factors for productive infection and propagation. We further applied an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from this screen. Using various in vitro HCV model systems and functional genomics approaches, we identify and characterize multiple novel host factors or pathways required for various steps of HCV life cycle. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allow the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. We further extended the genome-wide screen to microRNAs. We identified novel microRNA-controlled pathways and complex interactive regulatory networks that are involved in HCV infection and host response. Finally a cell-based high-throughput assay modified from our siRNA screening platform was developed and shown to be suitable for high-content screen of large libraries of pharmaceutical compounds. Novel anti-HCV probes have been identified and are currently under mechanistic investigation and therapeutic development. |
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