H5N1 bird flu viruses that have been circulating in U.S. dairy cattle have evolved some new mutations that help them attach more easily to cow cells, researchers report in a preprint published in BioRxiv. In the study, they say, they identified two genetic mutations in the viral surface protein that exploit a type of molecule uniquely abundant in cattle tissues, one that neither humans nor birds possess.
These mutations helped the virus grow better in cow mammary tissue, while they did not make it much worse at infecting human lung and nasal cells, says researchers in the paper.
To infect cells, influenza viruses latch onto sugars coating cell surfaces. Most H5N1 viruses are built to grab the sugar found in birds. But as the virus circulated through dairy farms, two mutations — labeled D104G and V147M — emerged repeatedly and independently across different herds, until they were present in nearly all cattle H5N1 viruses sampled. These mutations allow the virus to grip N-glycolylneuraminic acid, or NeuGc, a sugar that cattle produce abundantly across their mammary and respiratory tissues, but which is entirely absent in humans and birds.
To understand this, Thomas Peacock at Imperial College London and his colleagues first examined cattle tissues and found that the viruses were loaded with NeuGc-containing sugars, almost as abundant as the conventional ones the virus was already targeting. When the team tested viruses carrying these mutations against cattle mammary tissue in the lab, they replicated far more efficiently than earlier H5N1 strains. In human nasal and lung cells, however, the same mutations had little effect or slightly reduced viral growth.
However, the cattle-adapted viruses haven’t abandoned their ability to infect humans — they have simply gained an additional capability. “These mutations broaden receptor usage rather than switch specificity,” the team writes. “Host-specific modifications of sialic acids can act as powerful evolutionary filters shaping influenza receptor usage during mammalian emergence,” they add.
Journal Reference: BioRxiv. DOI: 10.64898/2026.04.02.715584
