Analysis of epigenetic regulation in immune responses against influenza virus infection

• Project/Area Number: 18K16184
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Nishioka Keisuke 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50790713)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: インフルエンザ / エピジェネティクス / 細菌叢 / インフルエンザウイルス / 免疫応答

Outline of Final Research Achievements

The involvement of epigenetic states in influenza virus infection was evaluated using multiple respiratory epithelial cell lines with same genetic backgrounds and epigenetic states at specific sites affected influenza virus infection was revealed.
Demethylation of the IFN-β promoter region promoted IFN-β production and induced protection against viral infection. Other regions may be involved, suggesting that induction of changes in the epigenetic state can contribute to the prevention of infectious diseases.

Academic Significance and Societal Importance of the Research Achievements

インフルエンザは毎年ワクチン接種が大規模に行われているものの、冬季には多数の患者が発生し、重症化すると多くのケースで致死率が高い呼吸器疾患を続発する。そのため重症化に関与する因子の解明は重要な課題である。本研究の成果は、生活習慣でも変化するエピジェネティックステートがウイルスに対する感染防御を誘導することが示唆されており、今後特定部位のエピジェネティックステートの変化を誘導することで新規の感染症予防法確立へ貢献できる可能性がある。

Research Products

• [Journal Article] Proteins produced by Streptococcus species in the lower respiratory tract can modify antiviral responses against influenza virus in respiratory epithelial cells (2021)
  • Author(s): Nishioka Keisuke、Kyo Michihito、Nakaya Takaaki、Shime Nobuaki
  • Journal Title: Microbes and Infection Volume: 23 Issue: 1 Pages: 104764-104764
  • DOI: 10.1016/j.micinf.2020.09.010
  • Peer Reviewed / Open Access
• [Journal Article] Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome (2019)
  • Author(s): Kyo Michihito、Nishioka Keisuke、Nakaya Takaaki、Kida Yoshiko、Tanabe Yuko、Ohshimo Shinichiro、Shime Nobuaki
  • Journal Title: Respiratory Research Volume: 20 Issue: 1 Pages: 246-246
  • DOI: 10.1186/s12931-019-1203-y
  • Peer Reviewed / Open Access
• [Journal Article] Demethylation around the transcriptional start site of the IFN-β gene induces IFN-β production and protection against influenza virus infection (2019)
  • Author(s): Nishioka Keisuke、Daidoji Tomo、Nakaya Takaaki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 520 Issue: 2 Pages: 269-276
  • DOI: 10.1016/j.bbrc.2019.09.136
  • Peer Reviewed / Open Access
• [Presentation] インフルエンザウイルス免疫応答に関与するエピジェネティックステートの解析 (2019)
  • Author(s): 西岡 敬介
  • Organizer: 日本ウイルス学会