Identification of cellular genes that affect host range restriction of influenza virus

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Influenza viruses pose a pandemic threat to human health because avian influenza viruses can sometimes acquire the ability to replicate in and transmit between people. Since humans have no pre-existing immunity to these strains, the whole world is susceptible and the virus spreads rapidly causing excess morbidity and mortality. The way in which this might happen is for a strain of bird flu to acquire a mutation in its genetic makeup that helps it replicate faster in human cells. We know about some of the mutations by which this switch is achieved, but we do not understand the mechanism behind them. In this project we will identify genes from the chicken and from the human host which might be important in determining whether a particular virus can replicate in either host. Then we will design experiments to discover why they are important for influenza virus replication. This basic scientific information will allow us to understand how to predict which strains of virus are the ones most likely to cause pandemics, and will also assist design of novel antiviral compounds that target essential steps of the virus cycle.