Pandemic influenza risk prediction based on searching compensatory mechanism

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21723
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 58:Society medicine, nursing, and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Watanabe Yohei 京都府立医科大学, 医学(系)研究科(研究院), 講師 (50452462)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 国際感染症 / 新興ウイルス / インフルエンザ / 宿主適応

Outline of Final Research Achievements

We compared changes in HA property before and after introducing host-adaptive mutations between influenza viruses that historically caused pandemics in the past (H1N1/H3N2 subtypes) and those that are highly pathogenic but have not yet become pandemics (H5N1 subtype). The results showed that, in H1N1/H3N2-HA, acquisition of human-type receptor binding specificity by mutagenesis is not accompanied by compensatory changes in membrane fusion pH threshold and HA structural stability, and its characteristics are significantly different from those in H5N1-HA. Additional analyses of mutation groups for PB2 and NA genes showed that some mutations enhance replicative advantage and remaining others reduce it, suggesting that coordination and tune-up by multiple gene mutations are important for pandemics emergence.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

「高病原性インフルエンザウイルスがパンデミック化するのか」という問いに対する科学的根拠は少ない。本研究の遂行によって、宿主適応過程におけるH5N1-HAの特性変化が過去にパンデミックを起こしたH1N1/H3N2-HAとは異なる可能性が示された。得られた知見はパンデミックインフルエンザに対するさらなる理解と今後のパンデミック対策へのより効果的な施策に役立つものと考えられる。