The role of influenza virus gene constellation and viral morphology on cytokine induction, pathogenesis, and viral virulence.

1. H5N1 viruses that cause severe disease in humans are potent inducers of proinflammatory cytokines in contrast to seasonal influenza viruses, and this may play a role in the mechanism of H5N1 pathogenesis. 2. H5N1 viruses are predominantly spherical in morphology. Virus morphology does not influence the ability to induce proinflammatory cytokines. 3. The NS1 viral protein may play a role in the potency of proinflammatory induction. 4. The H5N1 haemagglutinin and neuraminidase do not appear to transfer the high cytokine phenotype. 5. The ability to induce cytokines is a polygenic trait, involving a combination of different viral genes.