A single residue in the yellow fever virus envelope protein modulates virion architecture and antigenicity.

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Nat Commun. 2025 Sep 26;16(1):8449. doi: 10.1038/s41467-025-63038-5

Bibby S, Jung J, Low YS, Amarilla AA, Newton ND, Scott CA, Balk J, Ting YT, Freney ME, Liang B, Grant T, Coulibaly F, Young P, Hall RA, Hobson-Peters J, Modhiran N, Watterson D

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Abstract

Yellow fever virus (YFV) is a re-emerging flavivirus that causes severe hepatic disease and mortality in humans. Despite being researched for over a century, the structure of YFV has remained elusive. Here we use a chimeric virus platform to resolve the first high resolution cryo-EM structures of YFV. Stark differences in particle morphology and homogeneity are observed between vaccine and virulent strains of YFV, and these are found to have significant implications on antibody recognition and neutralisation. We identify a single residue (R380) in the YFV envelope protein that stabilises the virion surface, and leads to reduced exposure of the cross-reactive fusion loop epitope. The differences in virion morphology between YFV strains also contribute to the reduced sensitivity of the virulent YFV virions to vaccine-induced antibodies. These findings have significant implications for YFV biology, vaccinology and structure-based flavivirus antigen design.

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A single residue in the yellow fever virus envelope protein modulates virion architecture and antigenicity.

Abstract

PMID: 41006244 [PubMed - indexed for MEDLINE]

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