Nature Medicine | 2026
17 April 2026
A recent study published in Nature Medicine reveals the emergence and rapid expansion of a new highly pathogenic avian influenza (HPAI) A(H5N1) reassortant, designated as genotype D1.1, which became the predominant strain in North American wild birds during the autumn 2024 migratory season. First detected in September 2024, the D1.1 genotype spread with remarkable speed across multiple migratory flyways, nearly replacing previously circulating H5 genotypes by December 2024. This rapid genotypic sweep coincided with several significant spillover events, including detections in dairy cattle and 17 reported human cases, four of which were severe and two fatal.
The success of the D1.1 genotype appears to be driven by a combination of genomic and ecological factors. Researchers identified that D1.1 possesses a distinct North American-derived neuraminidase (NA) segment, which may provide an antigenic advantage due to lower existing population immunity compared to earlier strains. Furthermore, the timing of its emergence during the southward migration allowed for rapid viral amplification among high densities of immunologically naive juvenile birds at staging areas. Ecological stressors, such as persistent drought and altered habitat use, also likely facilitated increased interspecies transmission by forcing higher bird densities at remaining water sources.
Critically, the study found that while the D1.1 viruses in human cases exhibited specific mammalian-adaptive mutations, such as the HA E190D and Q226H substitutions, these markers were entirely absent in the sequences collected from wild birds. This suggests that such adaptations are likely arising de novo during individual human infections rather than circulating widely in the wild bird population. Additionally, receptor binding assays confirmed that the wild bird viruses maintain a strong affinity for avian-like receptors with little to no affinity for human-like receptors, indicating that the current risk of sustained human-to-human transmission remains low.
