University of Queensland researchers have captured the first high-resolution images of the yellow fever virus (YFV), a potentially deadly viral disease transmitted by mosquitoes that affects the liver.
They’ve revealed structural differences between the vaccine strain (YFV-17D) and the virulent, disease-causing strains of the virus.
Dr Summa Bibby from UQ’s School of Chemistry and Molecular Bioscience said despite decades of research on yellow fever, this was the first time a complete 3D structure of a fully mature yellow fever virus particle had been recorded at near-atomic resolution.
“By utilising the well-established Binjari virus platform developed here at UQ, we combined yellow fever’s structural genes with the backbone of the harmless Binjari virus and produced virus particles that could be safely examined with a cryo-electron microscope,” Dr Bibby said.
“The particles of the vaccine strain had a smooth and stable surface layer, while the particles of the virulent strain had bumpy uneven surfaces.”
The differences change how the body’s immune system recognises the virus.
“The bumpier, irregular surface of the virulent strains exposes parts of the virus that are normally hidden, allowing certain antibodies to attach more easily,” Dr Bibby said.
“The smooth vaccine particles keep those regions covered, making them harder for particular antibodies to reach.”
Yellow fever is a major public health concern in parts of South America and Africa and with no approved antiviral treatments, vaccination is the primary means of prevention.
Professor Daniel Watterson said the discovery provides crucial new insights into yellow fever biology and opens the door to improved vaccine design and antiviral strategies for it and other orthoflaviviruses.
“The yellow fever vaccine remains effective against modern strains and seeing the virus in such fine detail lets us better understand why the vaccine strain behaves the way it does,” Professor Watterson.
“We can now pinpoint the structural features that make the current vaccine safe and effective.
“The findings could even inform future vaccine design for related viruses like dengue, Zika and West Nile.”
The research was published in Nature Communications .
Nature Communications
Imaging analysis
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A single residue in the yellow fever virus envelope protein modulates virion architecture and antigenicity
26-Sep-2025
N.D.N., R.A.H., J.H.-P. and D.W. are inventors on patent application WO/2018/176075, relating to the chimeric BinJV platform. The remaining authors declare no competing interests.