ArticleNature communications2026
Polymerase mutations underlie early adaptation of H5N1 influenza virus to dairy cattle and other mammals.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- The mouse-lethal H5N1 influenza virus carrying the PB2-384L/443R/460M characteristics acquired in avian hosts can effectively utilize human ANP32A/B proteins.Emerging microbes & infections · 2026Article
- In silico analysis of pH stabilising mutations of hemagglutinin of influenza A virus H5N1 clade 2.3.4.4b.Npj viruses · 2026Review
- Mammary Gland Tropism and Milk-Mediated Transmission of H5N1 in Dairy Cattle: Implications for One Health Surveillance.Veterinary sciences · 2026Review
- High pathogenicity avian influenza A (H5N1) viruses isolated from poultry and wild birds in Japan during the 2024-2025 season.Microbiology spectrum · 2026Article
- Cellular tropism of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses in human respiratory and bovine mammary epithelial cells.Microbiology spectrum · 2026Article
- Evolutionary constraints limit additional mammalian adaptation of bovine-derived H5N1 influenza viruses in ferrets.bioRxiv : the preprint server for biology · 2026Article
- Cattle and human organoids reveal 2.3.4.4b H5N1 cross-species transmission potential and neuraminidase-specific neutralizing antibodies in humans.Nature communications · 2026Article
- Dairy cows infected with influenza A(H5N1) reveals low infectious dose and transmission barriers.Nature communications · 2026Article
- Variable transmission efficiency of mammalian origin HPAI D1.1 H5N1 strains in ferrets.bioRxiv : the preprint server for biology · 2026Article
- Primary bovine embryonic fibroblasts demonstrate variable fitness following infection with highly pathogenic avian influenza H5N1 strains and are susceptible to a recently circulating human 2009 pandemic lineage H1N1 strain.Microbiology spectrum · 2026Article
- The emergence and molecular evolution of H5N1 influenza viruses in United States dairy cattle.bioRxiv : the preprint server for biology · 2026Article
- Postinfection Pig and Ferret Antisera Show Similar Antigenic Profiles for Human Influenza A(H1N1pdm09) Viruses.Influenza and other respiratory viruses · 2026Article
- Pathogenesis of H5N1 Clade 2.3.4.4b in dry Jersey cows following intramammary inoculation shows within-host compartmentalization.bioRxiv : the preprint server for biology · 2026Article
- Advancing A(H5N1) influenza risk assessment in ferrets through comparative evaluation of airborne virus shedding patterns.Nature communications · 2026Article
- An outbreak of highly pathogenic avian influenza H5N1 could impact the dairy cattle sector and the broader economy in the United States.Communications earth & environment · 2026Article
- Structural analysis of antigenic variation and adaptive evolution of the H5N1 neuraminidase gene.PLoS computational biology · 2026Article
- Review
- The potential of H5N1 viruses to adapt to bovine cells varies throughout evolution.Nature communications · 2025Article
- Detection of clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus in a sheep in Great Britain, 2025.Emerging microbes & infections · 2025Article
- Identification of amino acid residues in polymerase PB2 responsible for differential replication and pathogenicity of avian influenza virus H5N1 isolated from human and cattle in Texas, US.Emerging microbes & infections · 2025Article
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25 authors.
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Abstract
In 2024, an unprecedented outbreak of H5N1 high pathogenicity avian influenza was detected in dairy cattle in the USA resulting in spillbacks into poultry, wild birds and other mammals including humans. Here, we present molecular and virological evidence that the cattle B3.13 genotype H5N1 viruses rapidly accumulated adaptations in polymerase genes that enabled better replication in bovine cells and tissues, as well as cells of other mammals including humans. We find evidence of several mammalian adaptations in cattle including PB2 M631L, which is found in all cattle sequences, and PA K497R, which is found in the majority. Structurally, PB2 M631L maps to the polymerase-ANP32 interface, an essential host factor for viral genome replication. We show that this mutation adapts the polymerase to better interact with bovine ANP32 proteins, particularly ANP32A, and thereby enhances virus replication in bovine mammary systems and primary human airway cultures. We show that ongoing evolution in the PB2 gene, including E627K and a convergently arising D740N substitution, further increase polymerase activity and virus replication in a range of mammalian cells. Thus, circulation of H5N1 in dairy cattle allows virus adaption improving replicative ability in cattle and poses a continued risk of zoonotic spillover.
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