A single residue in the yellow fever virus envelope protein modulates virion architecture and antigenicity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41006244.
- Also identified by DOI 10.1038/s41467-025-63038-5 and PMC identifier 12475062.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>17D</sub> 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.
Medical subject headings
- Yellow fever virus
- Viral Envelope Proteins
- Virion