[18-EEID US-UK DDCOVMP] Drivers of diversity and transmission of co-circulating viral lineages in host meta-populations

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Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is endemic in the USA, Asia and Europe, including the UK, and is considered the most important disease to control in swine populations. There are two distinct genotypes: PRRSV-1 mostly found in Europe and Asia, and PRRSV-2 predominating in the Americas but also in Asia and Europe. Additionally PRRSV-2 has also evolved a highly pathogenic type, which has now spread from China to other Asian countries. Vaccines against PRRSV-1 and PRRSV-2 exist, but due to the host response to PRRSV and since PRRSV is a rapidly evolving RNA virus with wide genetic variation and multiple sub-lineages, vaccines cannot be assumed to be fully protective.In this collaborative US-UK project we will investigate how ongoing viral evolution and variable cross-immunity to different viral strains influences circulation of these rapidly evolving viruses. In particular we will evaluate how partial immunity influences evolution within and between hosts using an experimental study, where quasi-species evolution will be tracked via next generation sequencing. To quantify viral evolution and patterns of repeated invasions of different viral lineages in field settings we will monitor farms and whole genome sequence the strains over time. We will also quantify how spatial heterogeneities in cross-immunity (based on previous infection and vaccination) and population connectivity influence co-circulation and interactions among viral lineages using a dataset of exceptional spatiotemporal resolution that covers ~20% of the U.S. sow population. Finally we will use this knowledge to perform simulation modelling to elucidate how spatial and temporal variation in cross-immunity influences evolutionary dynamics of co-circulating PRRSV lineages in realistic scenarios, which will ultimately enable us to predict what the risks of infection are to up coming PRRSV strains, and thus aid selection of the most appropriate vaccines as part of PRRSV control strategies.