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H5N1 Has Learned to Grip a Cattle Sugar That Humans and Birds Do Not Make

A bioRxiv preprint posted April 6 and summarized by Science News on April 14 identifies two mutations in the B3.13 cattle-adapted H5N1 strain (D104G and V147M in the haemagglutinin) that let the virus grip N-glycolylneuraminic acid, or NeuGc, a sialic acid made by cattle but not by humans or birds. [1] [2] Glycomic profiling of bovine mammary tissue showed it is enriched in NeuGc-capped glycans. The early cattle H5 viruses poorly recognized NeuGc. The new mutations allow efficient engagement of both NeuAc (the human-and-bird sialic acid) and NeuGc, without meaningfully attenuating replication in human lung or primary nasal epithelial cells. [2]

The cross-potential line is the one the paper makes cautiously. Pigs, sheep, and horses also make NeuGc. A virus that has learned to use NeuGc in cattle may find similar receptors in those species. The authors do not claim the jump is easy. They claim the receptor geometry is compatible in a way it was not before, and note that pigs in particular are the classical mixing-vessel concern because they express both NeuAc and NeuGc. [1]

For humans, the short-term risk is not increased. Lab tests found the NeuGc-grasping H5N1 either unchanged or slightly hindered in human nasal-cell growth. [1] The viruses reach higher levels in cattle, which means more virus in the environment of workers, milk tankers, and barn air. More virus is more exposure is more chances for further adaptation. The paper's value is naming what has already happened at the receptor level without hyperbole. The question at the species level is what comes next.

-- KENJI NAKAMURA, Tokyo

Sources & X Posts

News Sources
[1] https://www.sciencenews.org/article/mutations-h5n1-bird-flu-adapt-cows
[2] https://www.biorxiv.org/content/10.64898/2026.04.02.715584v1.full.pdf+html

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