Since 2021, highly pathogenic avian influenza viruses (HPAIVs) belonging to H5N1 clade 2.3.4.4b have circulated widely in North American wild birds and repeatedly spilled over into mammals. In 2025, the first H5N1-associated deaths in humans were recorded in the Western hemisphere, raising questions about how the ongoing evolution of the virus in wild birds impacts spillover risk. Here, our analysis of 21,471 H5N1 genomes identified an evolutionary shift in mid-2024, driven by interhemispheric migration from Asia and reassortment with new antigens. The genotypes that dominated the early years of North America's H5N1 epizootic traced their ancestry back to Europe, but Asia was the source of new "D1.1" genotype viruses that (a) spread faster, (b) have higher reassortment potential, (c) a broader host range, (d) repeatedly spill over to bovines, and (e) cause severe disease in humans, including non-farm workers.
Structured evidence records
Evidence records
6 total
Spillover Event2 records
Spillover EventExtraction confidence 0.95
Key finding
H5N1 avian influenza viruses circulating in wild birds in North America spilled over into mammals.
Since 2021, highly pathogenic avian influenza viruses (HPAIVs) belonging to H5N1 clade 2.3.4.4b have circulated widely in North American wild birds and repeatedly spilled over into mammals.
Transmission direction
animal-to-human
Geographic raw
North America
Spillover EventExtraction confidence 0.95
Key finding
D1.1 genotype H5N1 viruses spilled over to bovines and caused severe disease in humans.
The genotypes that dominated the early years of North America's H5N1 epizootic traced their ancestry back to Europe, but Asia was the source of new 'D1.1' genotype viruses that ... repeatedly spill over to bovines, and cause severe disease in humans, including non-farm workers.
Transmission direction
animal-to-human
Geographic raw
North America
Cross Species Transmission1 records
Cross Species TransmissionExtraction confidence 0.90
Key finding
H5N1 D1.1 genotype avian influenza viruses transmitted from wild birds to bovines in North America.
The abstract notes that 'D1.1 genotype viruses ... repeatedly spill over to bovines,' indicating viral transmission from wild birds to bovines in North America.
Method
genome analysis; phylogenetic analysis
Study design
phylogenetic analysis
Transmission direction
animal-to-animal
Geographic raw
North America
Genomic Evolution1 records
Genomic EvolutionExtraction confidence 0.95
Key finding
Genomic analysis of over 21,000 H5N1 sequences revealed an evolutionary shift in 2024, producing the D1.1 reassortant lineage through interhemispheric migration and reassortment.
Our analysis of 21,471 H5N1 genomes identified an evolutionary shift in mid-2024, driven by interhemispheric migration from Asia and reassortment with new antigens.
Genes or proteins
antigens
Analysis methods
genome analysis; evolutionary analysis
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.90
Key finding
H5N1 D1.1 genotype viruses underwent reassortment introducing new antigens, resulting in faster spread, broader host range, and greater virulence in humans.
Our analysis of 21,471 H5N1 genomes identified an evolutionary shift in mid-2024, driven by interhemispheric migration from Asia and reassortment with new antigens. The new 'D1.1' genotype viruses spread faster, had higher reassortment potential, a broader host range, and caused severe disease in humans.
Recombination Or ReassortmentExtraction confidence 0.98
Key finding
The D1.1 H5N1 genotype in North America arose through reassortment with new antigens following migration from Asia, producing viruses with broader host range and spillover into mammals and humans.
Our analysis of 21,471 H5N1 genomes identified an evolutionary shift in mid-2024, driven by interhemispheric migration from Asia and reassortment with new antigens. The genotypes that dominated early years traced their ancestry back to Europe, but Asia was the source of new 'D1.1' genotype viruses that have higher reassortment potential, a broader host range, and repeatedly spill over to bovines and humans.
