The genetic and cellular basis of human to human transmission of influenza virus

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The trigger for moving from the current level of pandemic alert to the next is the recognition of sustained human to human transmission of a novel influenza virus through the community. Yet we understand little about how these viruses do transmit and why viruses that remain essentially avian-like do not. We hypothesize that a major factor is the cell tropism of influenza virus which differs in human airways between avian and human influenza strains. The ferret is the best animal model to study human influenza. In this project a series of recombinant viruses that differ only their airway tropism will be generated and their transmission properties quantified. The findings will be related to viruses that bear H5N1 surface antigens. The contribution of other viral genes to transmissibility of humanized avian influenza viruses in ferrets will also be assessed.