Research for innate immune system sensor molecules in HBV infection

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K19324
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: NAKAI MASATO 北海道大学, 大学病院, 助教 (40756003)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: B型肝炎ウイルス / DNAセンサー

Outline of Final Research Achievements

In acute HBV infection phase, it takes time for the virus to grow and liver damage to appear, but the nucleic acid recognition for HBV-DNA and mechanism of innate immunity during that period are not well understood. In chronic HBV infection, immunologically tolerated state is established, and complete elimination of the virus is difficult because HBV covalently closed circular DNA (cccDNA) remains in the nucleus for life. Based on the above,the purpose of this study was to investigate the role of intracellular DNA sensor molecules in HBV infection, the effect on HBV-DNA replication, and the immune response. Focusing on various DNA sensor molecules, especially DDX41, we analyzed the expression in various hepatocyte cell lines, In NTCP-C4-HepG2 cells in which DDX41 was constitutively knocked down, HBV-DNA and RNA increased in an early stage compared with the control. This results suggested that DDX41 suppresses HBV proliferation in hepatocytes.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

HBVの完全な排除はまだ臨床的に達成されていないこと、その自然免疫応答はいまだ理解されていない点が多い。本研究ではDDX41分子がHBV感染に関与していることが示唆されるデータを得られている。DDX41のHBV感染に関しての報告は多くないため、本研究をさらに進めることで、HBV感染へのDDX41の関与を明らかにし、自然免疫応答やウイルス排除へのさらなる知見の蓄積が可能となる可能性がある。