Genomic analysis reveals how bird flu jumped from wild birds to poultry and people

By Dr. Liji Thomas, MDReviewed by Lauren HardakerMay 27 2025

A novel bird flu genotype is driving a surge in outbreaks across wild birds, poultry, and even a human in British Columbia, raising urgent questions about how this virus is evolving and what it means for future pandemic preparedness.

Study: Highly Pathogenic Avian Influenza A(H5N1) in Wild Birds and a Human, British Columbia, Canada, 2024. Image credit: Amy Lutz/Shutterstok.com

Avian influenza, also known as bird flu, is an emerging global pathogen that primarily affects birds but can occasionally spill over into humans. The most common strain found in poultry is highly pathogenic avian influenza (HPAI), specifically the H5N1 subtype.

Introduction

In the fall of 2021, a B strain of the HPAI clade 2.3.4.4b was transmitted to wild and domestic birds in Canada. Birds in eastern Canada brought it via the East Atlantic Flyway. The virus subsequently spread across North America, with infected fowl detected in British Columbia in April 2022.

This led to three waves of avian influenza, commonly referred to as bird flu. Various viruses were isolated from different hosts, most of which arose from gene reassortment within the 2.3.4.4b clade.

Another viral event via the Pacific Flyway occurred in February 2022, causing the fourth wave. The dominant genotype this time was A3. With each successive wave, new genotypes were identified, and the dominant genotypes shifted.

The fourth wave was primarily associated with a novel D.1.1,3, which descended from the clade introduced in February 2022.

Both genotypes now infect numerous wild birds in the province. The virus has spilled over into domestic fowl multiple times. With each wave, infection rates among wild birds and poultry continued to increase. As noted in the dispatch published in the journal Emerging Infectious Diseases, these waves were also characterized by the emergence of new genotypes and ongoing shifts in viral dominance.

Findings

The dominant D1.1 genotype was the focus of the current investigation into its ecology and origins. Data were collected as part of the British Columbia Wildlife Avian Influenza Surveillance Program. Researchers collected oropharyngeal and cloacal swabs from dead wild birds. A conserved gene common to all H5N1 genotypes was analyzed, along with whole-genome sequencing.

Approximately 69% of the new cases were from the Fraser Valley in British Columbia. Cackling geese (Branta hutchinsii) accounted for 35% of the cases, while Canada geese (Branta canadensis) and snow geese (Anser caerulenscens) comprised about 17% each.

Fewer than three cases were identified in other wild birds, such as American pigeons, bald eagles, barred owls, great horned owls, red-tailed hawks, and peregrine falcons.

Conditions in the Fraser Valley provide an optimal habitat for migrating waterfowl to spend the winter and support large-scale poultry farming. This may explain the higher rate of HPAI infection compared to the rest of Canada.

From October 3 to November 8, 2024, 57 wild bird samples containing 2.3.4.4b viruses were collected; six were of genotype A3, and the remaining 51 were of genotype D1.1.  The A3 isolates were phylogenetically closer to the 2024 A3 virus isolates from Japan than the 2023 A3 isolates from British Columbia. This suggests a recent introduction of HPAI from East Asia.

After November 8, 2024, an adolescent from Fraser Valley was diagnosed with D1.1 bird flu.

Between October 21 and November 30, 2024, 60 HPAI infections in poultry were reported, with 59 cases attributed to the D1.1 strain. This genotype has also been isolated from some parts of the United States south of British Columbia.

D1.1 has a unique NA segment

Phylogenetically, the D1.1 strain is most closely related to strains from wild birds. It comprises four segments, each derived from both Eurasian and North American versions. The neuraminidase [NA] segment was identified for the first time in this clade in British Columbia.

Interestingly, the 2024 D1.1 viruses share a recent common ancestor with the 2023 A3 viruses. However, they have fewer substitution mutations than expected over this period. This observation may indicate that the D1.1 genotype, or its ancestors, persisted in an environmental reservoir, such as frozen wetlands, over the summer of 2024 before being reintroduced into migratory birds in the fall. Alternatively, the virus may be particularly well adapted to certain wild bird populations, resulting in minimal evolutionary pressure and low genetic divergence.

Several infected poultry exhibited a D1.1-specific Am4N1 segment containing a mutation associated with antiviral resistance, NA-H275Y. These samples all came from a single outbreak. The mutation was not detected in wild birds. The possible functional impact of the Am4N1 neuraminidase segment on host-virus interactions is a subject for further investigation, as the study notes that certain NA lineages might increase viral shedding in wild birds. Given the rapid rise in poultry outbreaks caused by HPAI, increased environmental detections of the virus (such as from wetland sediment) in fall 2024 compared to fall 2023 may indicate that a larger number of birds were infected with D1.1, that D1.1 leads to greater viral shedding, or both.

Although cattle in the western United States have been infected with the B3.13 genotype, wild birds along the Pacific Flyway have not yet shown any signs of infection with the B genotype until fall 2024.

Conclusions

D1.1 appears to be an emerging genotype resulting from the reassortment of genes present in both Eurasian and North American lineages of the bird flu virus. It has been detected in wild birds, poultry, and one human to date.

The close genetic relationship of D1.1 strains isolated from humans and wild birds highlights the need for further research into the changes in the variant’s host range and infectious capability. The study also highlights that the reduced genetic divergence observed in D1.1, compared with similar viruses detected a year earlier, has implications for how molecular clock models are applied to track the evolution of HPAI viruses. This finding underscores the importance of ongoing genomic surveillance, including environmental monitoring, in enhancing our understanding of the mechanisms and risks associated with emerging avian influenza genotypes.​​​​​​​

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