Highly Pathogenic Avian Influenza Virus A/H5N1 Subclade 2.3.4.4b Isolated from a European Grey Seal (Halichoerus grypus) Is Highly Virulent in Ferrets

Highly pathogenic avian influenza A viruses subtype H5N1 (HPAIV H5N1), subclade 2.3.4.4b infect multiple avian and mammalian species, posing a potential pandemic risk. Here we describe the outcomes of infection of ferrets with an HPAIV H5N1 virus, isolated from a European grey seal in 2023, compared with an older HPAIV H5N1 (A/Indonesia/05/2005). Overall, infection of ferrets with A/grey seal/Netherlands/302603/2023 caused more rapid mortality than infection of ferrets with A/Indonesia/05/2005. Animals developed severe pneumonia and irreversible hypothermia, associated with high levels of virus replication and histopathological changes in the respiratory tract and peripheral organs. As animal models for severe avian influenza virus infections in humans play a key role in the development of intervention strategies against these infections, these findings highlight the importance of using updated ferret models based on circulating virus strains. Intratracheal infection with a H5N1 2.3.4.4b strain caused accelerated mortality in ferrets, characterized by severe pneumonia and irreversible hypothermia prior to death or euthanasia, associated with high levels of virus replication and histopathological changes in respiratory tract, liver, and spleen.