Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle in the United States.

Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird–to-cattle transmission episode. The movement of asymptomatic or presymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some 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 human populations. Editor's summary: High-pathogenicity avian influenza subtype H5N1 is now present throughout the US, and possibly beyond. More cattle infections elevate the risk of the virus evolving the capacity to transmit between humans, potentially with high fatality rates. Nguyen et al. show that from a single transmission event from a wild bird to dairy cattle in December 2023, there has been cattle-to-poultry, cattle-to-peridomestic bird, and cattle-to-other mammal transmission. The movement of asymptomatic dairy cattle has facilitated the rapid dissemination of H5N1 from Texas across the US. Evolution within cattle, assessed using deep-sequencing data, has detected low-frequency sequence variants that had previously been associated with mammalian adaptation and transmission efficiency. —Caroline Ash 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. The emergence and spread of highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b in dairy cattle in the US.: Highly pathogenic avian influenza (HPAI) H5N1 was detected in North America in late 2021, and epidemiological information and genomic analysis demonstrated a single spillover into dairy cattle by a reassorted HPAI H5N1 genotype B3.13 virus. The virus disseminated across the US through the movement of asymptomatic or presymptomatic animals and was subsequently reintroduced from dairy cattle back into other host species. [ABSTRACT FROM AUTHOR]