Abstract
In 1918 the Spanish influenza pandemic, caused by an avian H1N1 virus, resulted in over 50 million deaths worldwide. Several outbreaks of H7 influenza A viruses have resulted in human cases, including one fatal case. Since 1997, the outbreaks of highly pathogenic avian influenza (HPAI) of the H5N1 subtype have affected a wide variety of mammals in addition to poultry and wild birds. Here, we give an overview of the current knowledge of the determinants of pathogenicity of these three subtypes of avian influenza A virus in mammals. Common mechanisms for acquisition of virulence and replication of these avian influenza viruses in mammals are becoming apparent. Therefore, monitoring these and additional genetic changes upon zoonotic infections is important. Identification of genetic changes responsible for transmission between mammals will be an important task for the near future.