From feather to fur: spillover and spillback dynamics of H5N1 clade 2.3.4.4b at the gull–mink interface

The ongoing panzootic of H5N1 clade 2.3.4.4b high pathogenicity avian influenza virus (HPAIV) has increasingly affected non-traditional hosts like seabirds and mammals, including recent outbreaks in fur farms, in which transmission from infected gulls were suspected. To assess bird-to-mammal spillover and mammal-to-bird spillback dynamics, we performed experimental infections in yellow-legged gulls (Larus michahellis) and American minks (Neogale vison) using HPAIV strains isolated from gulls (H5N1/gull) and a farm mink outbreak (H5N1/mink). Minks challenged with H5N1/gull developed subclinical infection with limited shedding, but viral neurotropism in two out of four animals led to spontaneous emergence of key mammalian adaptation mutations in the brain, which demonstrates that H5N1 clade 2.3.4.4b spillover events from gulls to minks can lead to fast mammalian adaptation. In contrast, mammal-to-bird spillback, modelled by challenging gulls with the H5N1/mink strain, yielded no evidence of infection, suggesting a lower risk of sustained bird-mammal-bird transmission chains of 2.3.4.4b H5N1 HPAIV.