Analysis of virulence dterminants in full length H5N1 influenza genomes using computational modelling

Highly pathogenic avian influenza, particularly the H5N1 strain, has been the cause of several major outbreaks in Asian poultry and is a serious threat to human health for those exposed to diseased birds. The major concern is that through a few mutations it could become serious threat to the human population on a global scale. In this H5N1 project, we sought to understand which mutations caused the avian H5N1 virus to be especially pathogenic for mammals by analysing viral genome sequence data with sophisticated statistical methods. We found that whilst single mutations could have an effect, it was the combination of mutations that resulted in the most pathogenic strains. Importantly, it is not just the mutations on the easily testable surface proteins of the virus that can enhance pathogenicity, but mutations in the internal replication machinery proteins also have a significant effect.