Elucidation of host innate sensing mechanism for nucleic acid of hepatitis B virus that possibly cause liver cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870015
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology; Tumor therapeutics
• Research Institution: Hokkaido University
• Principal Investigator: SATO Seiichi 北海道大学, 遺伝子病制御研究所, 助教 (60459724)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: B型肝炎ウイルス / 自然免疫応答 / 核酸センサー / 抗ウイルス因子 / インターフェロン / RIG-I / シグナル伝達 / 肝臓癌

Outline of Final Research Achievements

In this study, we have revealed that HBV infection is sensed by the RIG-I protein through its recognition of certain viral RNA (pregenomic RNA) within the cells, which triggers a predominant production of type III interferons, a well-known antiviral protein. We further determined that a key element for the RIG-I-mediated recognition is the 5′-ε region of HBV pregenomic RNA, which was previously reported to take a stem-loop structure and serve as a binding site of HBV polymerase, an essential enzyme for viral propagation. In relation to this, we also discovered a novel role of RIG-I as a direct antiviral factor that can competitively inhibit the interaction of HBV polymerase with the 5′-ε region of viral genome. These findings indicated that RIG-I dually functions not only as an HBV sensor but also as a counteractor against viral polymerase in human hepatocyte, and also suggest that the ε region-derived RNA would be a therapeutic tool for the treatment of HBV infection.

Free Research Field

癌や感染を制御する自然免疫応答の分子基盤の解析