| International Session（Symposium）2(JSH・JSGE・JSGCS) |
| Thu. October 31st 14:30 - 17:00 Room 11: Portopia Hotel South Wing Topaz |
Comprehensive Functional Screening Using an in vitro HBV Infection Assay System to Identify Novel Antiviral Host Factors
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| Takuto Nosaka1, Masahiro Ohtani1, Yasunari Nakamoto1 | |||
| 1Second Department of Internal Medicine, University of Fukui | |||
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| Background: To cure hepatitis B virus (HBV) infection, it is essential to elucidate the function of hepatocyte host factors in regulating the viral life cycle. Hepatocyte STAT1 plays an important role in the immune response by transducing signals from interferons. Using an in vitro HBV infection assay system, we investigated the involvement of host factors that contribute to the control of viral infection by comprehensive functional screening. Methods: The in vitro HBV infection system was established using primary human hepatocytes (PXB cells) infected with HBV derived from a plasmid containing the 1.3-mer HBV genome. Comprehensive functional studies were performed using siRNA and vector transfection and analyzed using microarrays. Results: Knockdown of STAT1 decreased viral products in HBV-infected PXB cells. Microarray showed the STAT1 knockdown activated 21 metabolism-related pathways. FAH was extracted by siRNA of 43 genes in the pathways. FAH transfection inhibited HBV replication (P<0.05). Dimethyl fumarate (DMF), the methyl ester of FAH metabolite, showed antiviral effects without cytotoxicity by inducing autophagy (p62, ATG5/7) and anti-HBV-related genes (APOBEC3A/B/C). Conclusions: Independently of STAT1, FAH was identified as a host factor that contributes to the control of viral infection, and its metabolite, DMF, exhibited antiviral activity. The novel host factor FAH and its metabolites may be an innovative therapeutic strategy to control the HBV life cycle. |
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Index Term 1: FAH Index Term 2: Dimethyl fumarate |
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