Intra and inter-host evolution of equine and swine influenza viruses. (360G-Wellcome-088494_Z_09_Z)

There is a vast body of knowledge on the biology and epidemiology of Influenza viruses, but the relationship between epidemic processes and viral evolution at all scales is not well understood. A critical feature of this problem is the need to quantitatively link influenza dynamics at the individual and population levels. Current technologies of genome sequencing make tackling this problem feasible by allowing determination of the extent and structure of intra-host genetic variation of a viral p opulation within a single individual. Combining this with animal transmission studies makes it uniquely possible to consider how this variation is then transmitted in a natural host. In this application we propose a combination of whole genome sequencing and antigenic cartography studies, using equine and swine influenza viruses in their natural hosts, to understand essential issues such as i) the role of cross protective immunity in shaping viral diversity; and ii) the proportion of intra-host diversity that is passed at transmission. This project will provide a science base essential for understanding the implications of decisions made in the formulation of vaccines against all mammalian influenza viruses.