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

猪繁殖与呼吸综合征病毒(PRRSV)在美国、亚洲和欧洲(包括英国)流行，被认为是猪群中最需要控制的疾病。有两种不同的基因类型：PRRSV-1主要出现在欧洲和亚洲，PRRSV-2主要出现在美洲，但也存在于亚洲和欧洲。此外，PRRSV-2还进化出了一种高致病性的病毒类型，目前已从中国传播到其他亚洲国家。针对PRRSV-1和PRRSV-2的疫苗是存在的，但由于宿主对PRRSV的反应，以及由于PRRSV是一种快速进化的RNA病毒，具有广泛的遗传变异和多亚系，疫苗不能被认为是完全保护的。在这个美英合作的项目中，我们将研究正在进行的病毒进化和对不同病毒株的不同交叉免疫如何影响这些快速进化的病毒的循环。特别是，我们将使用一项实验研究来评估部分免疫如何影响宿主内部和宿主之间的进化，其中准物种进化将通过下一代测序进行跟踪。为了量化病毒进化和不同病毒谱系在野外反复入侵的模式，我们将监测农场和随着时间的推移对毒株进行全基因组测序。我们还将使用一个覆盖约20%的美国母猪种群的特殊时空分辨率的数据集，量化交叉免疫(基于先前的感染和疫苗接种)和种群连接方面的空间异质性如何影响病毒谱系之间的协同循环和相互作用。最后，我们将使用这些知识进行模拟建模，以阐明交叉免疫的空间和时间变化如何影响现实场景中共同循环的PRRSV谱系的进化动力学，这最终将使我们能够预测未来PRRSV毒株的感染风险，从而帮助选择最合适的疫苗作为PRRSV控制策略的一部分。

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.