Understanding the role of the viral polymerase in influenza virus virulence

‘A’ strain viruses cause annual epidemics that lead to about half a million deaths each year. Occasionally, highly pathogenic influenza A viruses, such as the Spanish Flu of 1918, emerge causing pandemics with an even higher death count. The reason for their pathogenicity is a dysregulated immune response, but the molecular mechanism that triggers this is not fully understood. Recent data show that the enzyme that copies the influenza virus genome, the RNA polymerase, may contribute to the induction of this strong immune response by creating large amounts of aberrant copies of the viral genome that can readily trigger an immune response. Interestingly, the RNA polymerases of highly pathogenic influenza A viruses produce vastly more of these aberrant products than the RNA polymerases of seasonal influenza viruses and a much stronger immune response as a result. This suggests a direct link between the activity of the RNA polymerase and the strength of the immune response.

This project aims to deliver a significant advance in our general understanding of influenza replication and why ostensibly simple differences between pathogenic and seasonal influenza A viruses lead to such dramatically different outcomes.