Adaptation of avian influenza virus polymerase to humans during pandemic emergence

Influenza viruses cause devastating pandemics when they emerge from animals and cross over into humans. In 1918, 50 million people died after being infected by the ‘Spanish’ influenza virus. Other viruses that emerge from animal sources such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Ebola virus also cause very severe disease in people. What is especially interesting about influenza is that once the new pandemic virus has infected nearly everyone, it evolves further to become a seasonal influenza virus associated with less severe disease, at least in previously healthy people.

We do not currently understand why the viruses that cross over to humans from animals are so lethal or how they adapt over time to become less severe. The explanation must be in the way the virus interacts with the host. In birds, influenza virus infection is silent but when an avian influenza infects humans, the mismatch between virus and host factors leads first to replication block and later to severe disease after some adaptive mutations.

I intend to discover the key host factors that underlie these observations. These might be excellent new targets for antiviral strategies. It will also assist with pandemic preparedness and therapeutic options for severe influenza.