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The #cow udder is a potential mixing vessel for #influenza A viruses

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By G.M.

 


Abstract

The incursion of high pathogenicity avian influenza A virus (IAV) into US dairy cows is unprecedented in the era of molecular diagnosis and pathogen sequencing. This raises questions over the likelihood of further outbreaks and whether dairy cattle could be a mixing vessel for novel strains of IAV. Using a panel of BSL2-safe reassortant viruses representing clade 2.3.4.4b H5 epizootic lineages circulating since 2020, we found that a cow B3.13 isolate displayed enhanced replication in cow mammary gland cells, along with increased viral polymerase activity and stronger interferon antagonism in cow cells compared to an earlier EA-2020-C genotype virus. However, multiple avian and mammalian IAV strains, including other clade 2.3.4.4b high pathogenicity genotypes, were replication competent in bovine cells, particularly those of the mammary gland, suggesting that there is a diverse circulating IAV pool with the potential to infect cows. Moreover, we show that cow mammary cells co-express alpha-2,3 and alpha-2,6 - linked sialic acids, and are susceptible to co-infection with human and avian IAVs. We conclude that the US cow influenza outbreak does not simply reflect a unique adaptation of the B3.13 genotype virus; rather, the bovine udder represents a permissive niche for IAV and a plausible site for reassortment, underscoring its potential role in generating novel influenza viruses with pandemic risk.


Competing Interest Statement

PD is a member of the UK government Department for Food, Environment and Rural Affairs (Defra) Science and Advisory Council subgroup on Emerging & Exotic Diseases (SAC-ED). He also holds a patent in the area of influenza vaccines. SdW is a member of the advisory committee of Avian Influenza and Newcastle Disease of the Dutch Ministry of Agriculture, Fisheries, Food Security and Nature.


Funder Information Declared

Biotechnology and Biological Sciences Research Council, BB/CCG2270/1, BBS/E/RL/230002A, BBS/E/RL/230002C, BBS/E/PI/230002B, BBS/E/PI/23NB0004, BBS/E/PI/23NB0003

Biotechnology and Biological Sciences Research Council, BB/V0119899/1, BB/T00875X/1

Natural Environment Research Council, NE/Y001591/1

Government of India, https://ror.org/036h6g940, BT/IN/Indo-UK/FADH/48/AM/2013

Medical Research Council, MR/Y03368X/1

Wellcome Trust, https://ror.org/029chgv08, 211222/Z/18/Z

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.08.29.673079v1

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