the evolution of influenza virus morphology and virulence

Seasonal influenza or 'the flu' causes 1-4 million cases of influenza and 350,000-650,000 deaths each year. The movement of exotic influenza viruses from animal hosts into humans has also caused four pandemics in the past century, causing >50 million deaths. There are three types of influenza currently circulating in humans: H1N1 influenza A, H3N2 influenza A and influenza B. Despite the immense disease burden caused by these viruses and an intensive research focus on them over many years, the differences in morphology and composition between these viruses remain unknown. It is also unclear whether viral morphology and composition change as influenza evolves or undergoes transmission from animal hosts to humans. Variations in influenza morphology and composition are important as they can impact a range of viral traits such as virulence and the potential of non-human influenza to cause a pandemic. It is also highly likely that changes in these traits will impact vaccine efficacy. In this proposal, we aim to describe the three types of human influenza virus in terms of protein composition, arrangement, binding capacity as well as genome structure. We aim to ascribe a genomic cause to any identified differences between the influenza viruses, or their associated strains, by computationally linking observed traits to associated genomic differences. These traits can then be reproduced in safer influenza viruses using reverse genetic systems via incorporation of the genomic feature associated with the trait to demonstrate the link. The proposal is interdisciplinary in nature, and highly relevant to ascertaining pandemic potential of influenza viruses as well as vaccine efficacy and design.