Study on DNA damage responses for regulation of intranuclear RNA viruses

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04083
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kyoto University
• Principal Investigator: Tomonaga Keizo 京都大学, ウイルス・再生医科学研究所, 教授 (10301920)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: RNAウイルス / 細胞核 / DNA損傷

Outline of Final Research Achievements

The aim of this study was to elucidate the interaction of DNA damage responses with replication of intranuclear replicating RNA viruses, such as Borna disease virus (BoDV). In this study, we found that IFI16, a DNA damage sensor molecule, recognizes nuclear replication of BoDV and triggers host immune responses. We also found that DNA-PK, which is involved in the DNA damage response, is localized at BoDV viral factories and of which activation affect BoDV replication. Furthermore, we showed that ADAR2, a nuclear RNA-editing enzyme that is also shown to be associated with DNA damage responses, contributes to avoidance of the innate immune response and the establishment of persistent infection by introducing A-to-G editing into the genomic RNA of BoDV.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究により、核内で増殖するボルナ病ウイルスが、宿主によりDNA損傷と認識され、細胞のDNA損傷反応を誘導するとともに、ウイルスが宿主のDNA損傷機構を利用して複製や感染を成立させている可能性を見出だした。本研究は、核内複製RNAウイルスが宿主ゲノムの損傷機構と関連することを示唆する初めての成果であり、今後、インフルエンザウイルスなどその他の核内複製RNAウイルスの複製阻害や病原性発現のメカニズムの解明へとつながる成果であると考えられる。