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Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle

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Abstract

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b virus has caused the death of millions of domestic birds and thousands of wild birds in the U.S. since January, 20221–4 Throughout this outbreak, spillovers to mammals have been frequently documented5–12. We report spillover of HPAI H5N1 virus in dairy cattle herds across several states in the U.S. The affected cows displayed clinical signs encompassing decreased feed intake, altered fecal consistency, respiratory distress, and decreased milk production with abnormal milk. Infectious virus and viral RNA were consistently detected in milk from affected cows. Viral distribution in tissues via immunohistochemistry and in situ hybridization revealed a distinct tropism of the virus for the epithelial cells lining the alveoli of the mammary gland in cows. Whole viral genome sequences recovered from dairy cows, birds, domestic cats, and a raccoon from affected farms indicated multidirectional interspecies transmissions. Epidemiologic and genomic data revealed efficient cow-to-cow transmission after apparently healthy cows from an affected farm were transported to a premise in a different state. These results demonstrate the transmission of HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface underscoring the ability of the virus to cross species barriers.

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Correspondence to Kiril M. Dimitrov or Diego G. Diel.

Supplementary information

Supplementary Discussion

This file contains Supplementary discussion that complements the discussion section of the main text, and Supplementary References.

Reporting Summary

Supplementary Table 1

RT-PCR data in CSV format showing testing results for Influenza A Matrix and H5-specific RT-PCR on all samples tested in the present study.

Supplementary Table 2

RT-PCR data in CSV format showing testing results for Influenza A Matrix and H5-specific RT-PCR on serial samples collected on days 3, 16 and 31 post-clinical diagnosis (pcd).

Supplementary Table 3

Mutational analysis in CVS format showing all amino acid mutations identified in PB2, PB1, PA, HA, NA, M (M1 and M2), NS (NS1 and NS2) gene segments of the highly pathogenic influenza A H5N1 virus sequences obtained in the present study. Predicted phenotype changes as reported through FluServer (GISAID) are also included.

Supplementary Table 4

List of sequences including GISAID accession numbers in CVS format used in the phylogenomic and mutational analyses conducted in the present study.

Supplementary Table 5

List of highly pathogenic influenza A H5N1 virus sequences obtained in the present study including GISAID accession numbers in CVS format and sample metadata (H5 clade classification, genotype, collection date, state, host, sample type and premise).

Supplementary Table 6

Mutational analysis in CVS format showing amino acid mutations that accumulated over time and identified in PB2, PB1, PA, HA, NA, NP and NS1 genome segments of highly pathogenic influenza H5N1 virus and their frequency among the available H5N1 sequences derived from cattle.

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Caserta, L.C., Frye, E.A., Butt, S.L. et al. Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle. Nature (2024). https://doi.org/10.1038/s41586-024-07849-4

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