Virulence determinants of high-pathogenic avian influenza viruses in gallinaceous poultry

High-pathogenic avian influenza viruses (HPAIV) cause devastating outbreaks in domestic poultry worldwide. Moreover, they repeatedly lead to severe, even fatal disease in humans, raising concerns about their pandemic potential. HPAIV have evolved from circulating low-pathogenic precursors in several independent events by spontaneous acquisition of a polybasic cleavage site in the hemagglutinin (HA) envelope protein. Remarkably, in nature, HPAIV are confined to the HA serotypes H5 and H7 from the 16 HA serotypes known in birds. However, experimental introduction of a polybasic cleavage site into non-H5/H7 HA may result in a highly pathogenic phenotype, indicating that emergence of HPAIV with novel serotypes is conceivable, but requires further adaptation to the chicken host.