Evaluation of mechanisms of increases in virus replication in bronchial epithelial cells from patients with chronic obstructive pulmonary disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15953
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kyushu University
• Principal Investigator: Kan-o Keiko (花村敬子) 九州大学, 大学病院, 医員 (50813771)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: PI3Kδ / インターフェロン / 抗ウイルス薬 / PD-L1 / HSP70

Outline of Final Research Achievements

Cigarette smoke exposure induces reactive oxygen species such as H2O2 in bronchial epithelium. We showed that treatment with H2O2 increased replication of human metapneumovirus by inducing heat shock protein 70.
We also showed that PI3Kdelta specific inhibitor suppressed synthetic double-stranded RNA poly I:C-induced the expression of co-inhibitory molecule PD-L1, and production of inflammatory cytokine and chemokines in murine lungs. In addition, PI3Kdelta specific inhibitor enhanced antiviral immune responses, production of type I and type III interferons, and inhibited replication of human metapneumovirus in bronchial epithelium.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

以前の研究において、慢性閉塞性肺疾患（COPD）患者の気道上皮細胞では健常者と比較してヒトメタニューモウイルス（hMPV）が増殖しやすいことを報告していた。本研究はその機序として活性酸素による熱ショックタンパク質70（Hsp70）の関与を示し、Hsp70阻害剤がCOPD増悪抑制薬・抗hMPV薬となる可能性を示した。
またPI3Kδ阻害剤は宿主の抗ウイルス免疫応答（インターフェロン産生）を増強し過剰な免疫応答を抑制することから、気道ウイルス感染症の治療薬となる可能性を示した。