| Project/Area Number |
19K23841
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0803:Pathology, infection/immunology, and related fields
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| Research Institution | Kanazawa University |
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Principal Investigator |
Lim Kee Siang 金沢大学, ナノ生命科学研究所, 特任助教 (60842987)
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Hemagglutinin / Influenza A / HS-AFM / Fusogenic transition / viral fusion protein / Influenz A / Virulence factor / High Speed AFM / Exosome |
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| Outline of Research at the Start |
Generation of HS-AFM simulated images of HA using data in RCSB PDB website.
HS-AFM recording for HA native structure and molecular dynamic in physiological buffers.
Direct visualization of transient conformational changes of HA in acidic conditions using HS-AFM.
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| Outline of Final Research Achievements |
The native conformation of human influenza A hemagglutinin (HA) observed using HS-AFM is ellipsoidal, and it undergoes fusogenic transition in acidic condition to become Y-shape. Direct real-time observation of fusogenic transition suggests that the transition mechanism is likely to fit to the Uncaging Model. HA-exosome interaction is weak in neutral condition but firm in acidic condition. The weak interaction could be mediated by HA-receptor (sialic acid) interaction. In contrast, the firm interaction implies that HA fusion peptide could be released after fusogenic transition, and then inserted into exosomal layer and resulted deformation or rupture of exosomes.
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| Academic Significance and Societal Importance of the Research Achievements |
This study could provide important insights that are essential for vaccine and antiviral drug developments to cope annual flu season in Japan. Besides, our study also suggest that HS-AFM is a feasible tool to complement other imaging tools and bioassays to enhance virology research in near future.
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