Elucidation of mechanisms involved in increased severety of influenza virus infection by using in vitro models of asthma and COPD

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16217
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Nakayama Misako 滋賀医科大学, 医学部, 助教 (00510306)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 気道上皮 / オルガノイド / 喘息 / 慢性閉塞性肺疾患 / COPD / インフルエンザウイルス / SARS-CoV-2 / 網羅的遺伝子発現解析

Outline of Final Research Achievements

In patients with asthma or COPD, influenza virus causes a sudden worsening of clinical symptoms. However, the mechanisms of the sudden worsening of clinical symptoms are not elucidated.
In primary small airway epithelial cells isolated from patients with asthma, gene expression of a sialytransferase that promotes the avian-type influenza virus receptor was upregulated compared to cells from COPD patients and healthy subjects. Of note, in a small airway organoid model, RNA-sequence analysis demonstrated genes differentially expressed between cells from asthma and COPD patients upon H1N1 and H5N1 influenza A viruses and SARS-CoV-2.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

喘息または慢性閉塞性肺疾患を有する患者ではインフルエンザウイルス感染によって重症化する危険性があることが知られる。本研究により、喘息と慢性肺疾患患者由来の小気道上皮では、インフルエンザウイルスに対する感受性や感染後の反応性が異なる可能性が示唆された。ウイルス感染が最初に成立するのは気道上皮であることから、気道上皮で感染を制御することにより、重症化を防ぐことが期待される。