Journal
NANO LETTERS
Volume 20, Issue 9, Pages 6320-6328Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c01755
Keywords
high-speed atomic force microscopy; influenza A; hemagglutinin; exosomes; fusogenic transition
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Funding
- MEXT/JSPS KAKENHI from MEXT Japan [19K23841, 20K16262, 17H05874, 17K08655]
- Kobayashi International Scholarship Foundation
- Shimadzu Science Foundation
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Influenza A hemagglutinin (HA) is one of the crucial virulence factors that mediate host tropism and viral infectivity. Presently, the mechanism of the fusogenic transition of HA remains elusive. Here, we used high-speed atomic force microscopy (HS-AFM) to decipher the molecular dynamics of HA and its interaction with exosomes. Our data reveal that the native conformation of HA in the neutral buffer is ellipsoidal, and HA undergoes a conformational change in an acidic buffer. Real-time visualization of the fusogenic transition by HS-AFM suggests that the mechanism is possibly fit to the uncaging model, and HA intermediate appears as Y-shaped. A firm interaction between the HA and exosome in an acidic buffer indicates the insertion of a fusion peptide into the exosomal layer and subsequently destabilizes the layer, resulting in the deformation or rupture of exosomes, releasing exosomal contents. In contrast, the HA exosome interaction is weak in a neutral buffer because the interaction is mediated by weak bonds between the HA receptor-binding site and receptors on the exosome.
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