Host range restriction and pathogenicity of influenza virus determined by respiratory epithelial inflammation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03475
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Kawaguchi Atsushi 筑波大学, 医学医療系, 教授 (90532060)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 炎症応答

Outline of Final Research Achievements

To understand the pathogenesis of influenza virus infection, it is necessary to distinguish between the inflammatory response in the airway epithelial tissues in the early stages of infection and the excessive inflammatory response amplified secondarily by macrophages. We identified MxA as a sensor molecule that regulates the induction of inflammatory response from airway epithelial cells, and found that MxA suppressed human infection with avian influenza virus, suggesting that MxA is one of the molecular determinants of host range restriction for avian influenza virus. We also revealed that ASC speckles released extracellularly by the inflammatory response are transmitted cell-to-cell and induce an excessive inflammatory response (cytokinesis storm) even in uninfected cells.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

MxAは鳥インフルエンザに対して、季節性インフルエンザよりも強く炎症応答を誘導することが明らかになり、季節性インフルエンザはMxAに対する逃避変異を獲得していることでヒトでの感染能・伝播能を獲得することが示唆された。また、ASCスペックルの細胞間伝播を制御することで、感染症による急性炎症だけでなく、喘息など慢性炎症も制御できることが明らかになり、新たな創薬標的を同定することができた研究成果である。