[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（Porcine Reproductive and Respiratory Syndrome Virus，PRRSV）是美国、亚洲和欧洲（包括英国）的地方病，被认为是猪群中最重要的疾病。有两种不同的基因型：PRRSV-1主要在欧洲和亚洲发现，PRRSV-2主要在美洲，但也在亚洲和欧洲。此外，PRRSV-2还进化成高致病性类型，现已从中国传播到其他亚洲国家。目前已有针对PRRSV-1和PRRSV-2的疫苗，但由于宿主对PRRSV的反应，以及PRRSV是一种快速进化的RNA病毒，具有广泛的遗传变异和多个亚系，疫苗不能被认为是完全保护性的。在这个美英合作项目中，我们将研究正在进行的病毒进化和对不同病毒株的可变交叉免疫如何影响这些快速进化的病毒的传播。特别是，我们将评估部分免疫力如何影响宿主内部和宿主之间的进化，使用实验研究，准物种进化将通过下一代测序进行跟踪。为了量化田间环境中不同病毒谱系的病毒进化和重复入侵模式，我们将监测农场并随时间推移对菌株进行全基因组测序。我们还将量化交叉免疫中的空间异质性（基于先前的感染和疫苗接种）和群体连通性如何影响病毒谱系之间的共循环和相互作用，使用的数据集具有特殊的时空分辨率，覆盖了约20%的美国母猪种群。最后，我们将利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在现实情况下共循环的PRRSV谱系的进化动力学，这将最终使我们能够预测即将到来的PRRSV毒株感染的风险，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.