INTRODUCTION
Highly pathogenic avian influenza (HPAI) viruses have critical consequences for animal health and the agricultural economy—and may have pandemic potential. HPAI related to the goose/Guangdong 2.3.4.4 hemagglutinin (HA) H5NX phylogenetic clade has spread to nearly 100 countries, and it is recognized as a panzootic. HPAI virus circulation is ongoing in North America, and after a trans-Atlantic incursion in late 2021, the HPAI H5N1 clade 2.3.4.4b virus caused widespread outbreaks. The outbreaks resulted in extensive mortality events, culling of poultry when detected in agricultural systems, and interspecies transmission events into mammals. It is critical to determine how HPAI clade 2.3.4.4b evolves in wild birds and in nonhuman mammals after spillover to assess the potential for human infection and transmission.
RATIONALE
In late January 2024, veterinarians observed dairy cattle displaying decreased feed intake and changes in milk quality and production. On 25 March 2024, HPAI H5N1 clade 2.3.4.4b was confirmed in dairy cattle in Texas. Shortly thereafter, the virus was identified in cattle in eight other United States (US) states by members of the National Animal Health Laboratory Network. The goal of this study was to analyze genetic sequence data collected after the introduction of HPAI H5N1 in late 2021 into the Atlantic flyway of North America and its onward circulation and reassortment with North American wild bird–origin low-pathogenicity viruses. These data were combined with whole-genome sequence data and epidemiological information from the HPAI H5N1 outbreak among US dairy cattle to help us understand when the interspecies transmission event to cattle occurred and the consequences of animal movement for virus spread.
RESULTS
H5N1 clade 2.3.4.4b genotype B3.13 influenza A virus was confirmed in milk with limited detections in nasal swabs. The initial outbreak included samples from 26 dairy cattle premises across eight states and six poultry premises in three states. The sequences isolated from cattle clustered within a single group in phylogenetic analyses, supporting a single spillover event in late 2023. A reassortment event preceded the spillover, and after introduction, the virus persisted in cattle with evidence for transmission from cattle into poultry and peridomestic animal species. Epidemiological records and phylodynamic modeling documented that the movement of asymptomatic or presymptomatic dairy cattle resulted in the dissemination of the virus across the US. We identified low-frequency within-host sequence variants across the genome that were associated with changes in virulence, host-range specificity, and mammalian adaptation.
CONCLUSION
A single wild bird-to-cattle transmission event of HPAI H5N1 clade 2.3.4.4b occurred in late 2023. The spillover was likely preceded by a reassortment event in wild bird populations followed by the movement of cattle that spread HPAI within the US dairy herd. Molecular markers that may lead to changes in transmission efficiency and phenotype were detected at low frequencies. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to humans and other host populations.