Rosa Rubicondior: Malevolent Designer News - Stunning 3D Images of the Yellow Fever Virus Reveal It's Irreducible Complexity

High-resolution imaging of yellow fever virus reveals structural secrets that could power next-generation vaccines.

UQ scientists uncover secrets of yellow fever - News - The University of Queensland
Scientists at the University of Queensland, Australia, have produced near atomic-level 3D images of the yellow fever virus. These reveal the remarkable complexity that Michael J. Behe and William A. Dembski of the Discovery Institute insist constitutes evidence of intelligent design – a theme almost universally endorsed by creationists and forming the central plank of their advocacy for creationism.

They have recently published their findings, open access, in the journal Nature Communications.

So, the obvious question for intelligent design advocates is this: is the irreducible complexity and complex specificity of the yellow fever virus evidence that it was intelligently designed to kill people? Or, when complex specified information and irreducible complexity do harm to humans, do these supposed ‘evidences’ for the existence of an intelligent designer (i.e. a god) somehow cease to apply, even though they benefit the virus? If so, how can a supposedly scientific definition change its meaning depending on the subjective judgement of what is being specified and how much or how little it benefits humans?

Yellow Fever Virus: A Quick Guide. Family and Structure
Yellow fever virus (YFV) belongs to the Flaviviridae family, the same group that includes dengue, Zika, and West Nile viruses. It is a single-stranded, positive-sense RNA virus enclosed in a spherical capsid and wrapped in a lipid envelope studded with the E (envelope) proteins that mediate host-cell entry.

Transmission
The virus is transmitted primarily by Aedes mosquitoes, especially Aedes aegypti. Humans usually become infected when bitten by an infected mosquito, but in forested regions transmission cycles also occur between mosquitoes and non-human primates.

Symptoms and Disease
After an incubation period of 3–6 days, infected individuals typically develop fever, headache, muscle pain, nausea, and fatigue. Most people recover, but around 15% progress to a severe form involving jaundice, internal bleeding, liver and kidney failure, and a high risk of death. Hence the name “yellow fever”.

Geographical Range
YFV is endemic in parts of tropical Africa and South America. Urban outbreaks can occur wherever Aedes mosquitoes thrive and vaccination rates are low.

Vaccination and Prevention
A highly effective live-attenuated vaccine has been available since the 1930s and provides long-term—often lifelong—immunity. Control strategies focus on vaccination, vector control, and surveillance of mosquito populations and primate reservoirs.

Evolution and Ecology
Genetically, YFV shows the typical evolutionary patterns of RNA viruses: high mutation rates and rapid diversification. Its complex interaction with both primate hosts and mosquito vectors has produced several distinct viral lineages, each adapted to local ecological conditions.

Details of the research are in a University of Queensland news item.

UQ scientists uncover secrets of yellow fever
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. The particles of the vaccine strain had a smooth and stable surface layer, while the particles of the virulent strain had bumpy uneven surfaces.

Dr Summa Bibby, first author.
School of Chemistry & Molecular Biosciences
The University of Queensland
St Lucia, QLD, Australia.

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. The smooth vaccine particles keep those regions covered, making them harder for particular antibodies to reach.

Dr Summa Bibby.

YFV virus structures.

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. 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.

Professor Daniel Watterson, co-corresponding author.
School of Chemistry & Molecular Biosciences
The University of Queensland
St Lucia, QLD, Australia.

Publication:
Bibby, S., Jung, J., Low, Y.S. et al.
A single residue in the yellow fever virus envelope protein modulates virion architecture and antigenicity.
Nat Commun 16, 8449 (2025). https://doi.org/10.1038/s41467-025-63038-5

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_17D 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.

Fig. 1: Structural and antigenic characterisation of bYFVs.

a Representative cryo-EM micrographs of purified bYFV_17D, bYFV_ES504 and bYFV_Asibi particles incubated at 4 °C prior to freezing. b Two-dimensional class averages of bYFV_17D and bYFV_ES504 particles. The displayed class distribution is shown as a percentage of the total number of particles. Cryo-EM density map of bYFV_17D (c) and bYFV_ES504 (d) with I3 symmetry applied. The maps are radially coloured according to the following: 0-150 Å red, 151-195 Å yellow, 196-210 Å green, 211-225 Å cyan, 226-240 Å blue Å. e IC50 values of recombinant hIgG1 anti-YFV or anti-flavivirus mAbs against bYFV_17D, bYFV_ES504 and bYFV_Asibi. Each symbol represents a technical replicate from three biological replicates (n = 6). f Serum neutralising titres of human YFV_17D vaccinees (n = 14) against bYFV_17D, bYFV_ES504 and bYFV_Asibi. In both (e) and (f), neutralisation was determined via FRNTs on C6/36 (Aedes albopictus) cells. Lines indicate group medians. Significance was determined via Kruskal-Wallis tests with Dunn’s multiple comparisons test on GraphPad Prism 9.0. ****p < 0.0001, ***p ≤ 0.0002, **p ≤ 0.002, *p ≤ 0.03. For 2C9: p = 0.006 (ES504 vs. Asibi), 2A10G6: p = 0.040 (17D vs. ES504) and p = 0.002 (17D vs. Asibi), 6B6C−1: p = 0.034 (17D vs. ES504) and p = 0.002 (17D vs. Asibi), 864: p = 0.0015 (17D vs. ES504 and 17D vs. Asibi), human vaccinee sera: p = 0.0001 (17D vs ES504) and p = 0.046 (17D vs Asibi). LOD = limit of detection. Source data is provided as a Source Data file.

Fig. 2: Cryo-EM of bYFV_17D and bYFV_ES504 complexed with 5A and 2C9 Fabs.

a Representative micrographs of bYFV_17D and bYFV_ES504 with and without complexing with 5A or 2C9 Fab. Viruses and Fabs were combined in a 1:1 ratio and incubated overnight at 4 °C prior to vitrification. b Cryo-EM density maps of bYFV_17D and bYFV_ES504 complexed with either 5A Fab or 2C9 Fab with I3 symmetry applied. Maps are radially coloured according to the following: 0-150 Å red, 151-195 Å yellow, 196-210 Å green, 211-225 Å cyan, 226-240 Å blue Å, 241-255 Å orchid. c Cryo-EM density map and atomic model of bYFV_17D complexed with 2C9 Fab. The density map was obtained via symmetry expanded ASU reconstruction and is shown in grey (E) and blue (variable region of 2C9 Fab), with the atomic model shown in red (E-DI), yellow (E-DII), blue (E-DIII) and grey (2C9 Fab). The N151 glycan is shown in green. d Top view of bYFV_17D:2C9 E dimer atomic model. e Comparison of the bYFV_17D:2C9 cryo-EM near-atomic resolution model and the YFV_17D X-ray crystal structure (PDB:6IW4) in pink. Dotted lines are illustrating the E protein curvature differences between these two models.

Fig. 4: Cryo-EM of bYFV_ES504/DIII_17D and bYFV_Asibi/DIII_17D.

a Cryo-EM density map of bYFV_ES504/DIII_17D with I3 symmetry applied and coloured according to its local resolution. b Cryo-EM reconstruction and atomic model of the bYFV_ES504/DIII_17D ASU. c Cryo-EM density map of bYFV_ES504/DIII_17D:2C9 with I3 symmetry applied and coloured according to its local resolution. d Cryo-EM reconstruction and atomic model of bYFV_ES504/DIII_17D:2C9 ASU. e Cryo-EM density map of bYFV_Asibi/DIII_17D with I3 symmetry applied and coloured according to its local resolution. f Cryo-EM reconstruction and atomic model of bYFV_Asibi/DIII_17D ASU. In (e) and (f) the pentagons, triangles, and ovals represent the icosahedral five-, three- and two-fold axes, respectively. In (b), (d), and (f) the density map was obtained via symmetry expanded ASU reconstruction using cisTEM2 and is shown in either grey (E) or blue (2C9 Fab), with the atomic models shown in red (E-DI), yellow (E-DII), blue (E-DIII) and grey (2C9 Fab). g IC50 values of recombinant hIgG1 anti-YFV or anti-flavivirus mAbs against the bYFV DIII chimeras. Neutralisation was determined via FRNTs on C6/36 (Aedes albopictus) cells. Lines indicate group medians, and each symbol represents a technical replicate from three biological replicates. For bYFV_17D/DIII_Asibi and bYFV_Asibi/DIII_17D against 5A n = 3, and for all other groups n = 6. Parental bYFV_17D and bYFV_Asibi controls are from Fig. 1E. bYFV DIII chimeras were compared to parental viruses by two-tailed Mann-Whitney tests on GraphPad Prism 9. **p ≤ 0.002. For 2A10G6: p = 0.002 (17D vs 17D/DIII_Asibi) and p = 0.004 (Asibi vs Asibi/DIII_17D), 6B6C−1 and 864: p = 0.002 (17D vs 17D/DIII_Asibi and Asibi vs. Asibi/DIII_17D). LOD = limit of detection. Source data is provided as a Source Data file.

Bibby, S., Jung, J., Low, Y.S. et al.
A single residue in the yellow fever virus envelope protein modulates virion architecture and antigenicity.
Nat Commun 16, 8449 (2025). https://doi.org/10.1038/s41467-025-63038-5

Copyright: © 2025 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

As ever, what this research truly demonstrates is not evidence of a supernatural designer but the power of natural processes operating over vast timescales. The yellow fever virus is no more “designed” than any other organism whose structure reflects the pressures of replication, mutation, host defences, and ecological constraints. Its intricacy is precisely what we expect from evolution by natural selection acting on an RNA virus with an exceptionally high mutation rate.

Creationists, meanwhile, are once again left trying to explain why the same features they claim point to a benevolent, omniscient designer somehow cease to be applicable when those features lead to human suffering. Evolution offers a consistent, evidence-based explanation for both the complexity of the virus and the disease it causes. Intelligent design offers nothing but special pleading.

Science continues to reveal the natural world in ever finer detail, and every such discovery further undermines the notion that complexity automatically implies design. What it actually implies is history: the long, blind, iterative history of evolution. And the more clearly we can see that history, the less room there is for the wishful thinking and contrived arguments on which creationism depends.

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