Genetic determinants for infectivity and pathogenicity of influenza viruses.

The objective of the studies presented was to define a molecular basis for infectivity and pathogenicity of influenza virus. It is demonstrated that activation of the HA glycoprotein by post-translational proteolytic cleavage is indispensable for the formation of infectious influenza virus. There are two preconditions for influenza virus to be pathogenic: (1) the presence on the virus particle of a cleaved HA molecule essential for the infectivity, and (2) an optimal genome composition. In naturally occurring avian influenza viruses there is a direct correlation between the cleavability of the haemagglutinin, the potential of the virus to be produced in infectious form in a wide range of host cells, and the viruses' pathogenicity for chicken. It is concluded that Nature selects an optimal gene constellation for each individual field strain. In these viruses the structure of the haemagglutinin is the determining factor for pathogenicity.