What Was the Biological Basis for 1918 Pandemic Virus Pathogenicity?
Sequence analysis alone does not offer clues to the pathogenicity of the 1918 virus. A series of experiments are under way to model virulence in vitro and in animal models by using viral constructs containing 1918 genes produced by reverse genetics. Influenza virus infection requires binding of the HA protein to sialic acid receptors on host cell surface. The HA receptor-binding site configuration is different for those influenza viruses adapted to infect birds and those adapted to infect humans. Influenza virus strains adapted to birds preferentially bind sialic acid receptors with α (23) linked sugars (2729). Human-adapted influenza viruses are thought to preferentially bind receptors with α (26) linkages. The switch from this avian receptor configuration requires of the virus only 1 amino acid change, and the HAs of all 5 sequenced 1918 viruses have this change, which suggests that it could be a critical step in human host adaptation. A second change that greatly augments virus bind
