US:UK Collab: Multi-scale infection dynamics from cells to landscapes: FMD in African buffalo

美国：英国合作：从细胞到景观的多尺度感染动态：非洲水牛的口蹄疫

• 批准号: 2208087
• 负责人: Anna Jolles
• 金额: $ 298.05万
• 依托单位: Oregon State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2208087&HistoricalAwards=false
• 关键词: US; UK; Collab; Multi; scale

The goal of this study is to determine if viral spread and persistence can be predicted from viral interactions with host cells. Predicting which viral genetic variant will be more harmful to hosts, which will spread widely, and which will persist in host populations is a major challenge. In this study, researchers from the United States, the United Kingdom, and South Africa will collaborate to investigate the spread of foot-and-moth disease virus (FMDV) in wild African buffalo by studying viral growth rate, life span, and the rate of cell destruction. This information can then be used to screen future variants and identify dangerous variants before they spread. The project will investigate spillover of FMDV into domestic cattle. It will also allow US graduate students and post-doctoral scholars to learn to collaborate internationally with students from the UK and South Africa.The team will investigate viral dynamics from genomic to landscape scales using foot-and-mouth disease viruses in their wildlife host, African buffalo, as a model system. FMDVs are some of the fastest-evolving and most contagious known pathogens, which cause enormous losses when they spillover from wildlife to livestock populations. FMDV variants from Kruger National Park, South Africa, have been collected and archived for over forty years, providing historical and phylogenetic context for evaluating lineages that are currently circulating in the park’s buffalo population. The researchers will create a data-driven mathematical framework linking viral dynamics across organizational scales, to test whether dynamics within hosts, at population and landscape scales, can be predicted from phenotypic variation among viral lineages. Using experiments, observational field studies and mathematical models, the team will: discover patterns of phenotypic differentiation among current and historic FMDV lineages, evaluate whether viral phenotypic traits measured in vitro predict viral dynamics in live hosts, explore how within-host viral and immune dynamics translate to FMD dynamics in buffalo herds, determine how variation among viral strains structures viral diversity at the landscape scale, and characterize genotypes and phenotypes of FMDV strains that caused outbreaks in livestock. The modeling framework will be tested to see whether the approach correctly distinguishes historic lineages that spread, diversified, and in some cases spilled over to livestock, from strains that petered out after modest periods of growth.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

本研究的目的是确定是否可以从病毒与宿主细胞的相互作用中预测病毒的传播和持久性。预测哪种病毒遗传变异对宿主的危害更大，哪种病毒将广泛传播，哪种病毒将在宿主群体中持续存在，这是一个重大挑战。在这项研究中，来自美国、英国和南非的研究人员将合作，通过研究病毒的生长速度、寿命和细胞破坏速度，调查口蹄疫病毒（FMDV）在非洲野生布法罗中的传播情况。然后，这些信息可以用于筛选未来的变体，并在它们传播之前识别危险的变体。该项目将调查口蹄疫病毒对家畜的溢出。该项目还将使美国研究生和博士后学者能够学习与英国和南非学生进行国际合作。该团队将以野生动物宿主非洲布法罗中的口蹄疫病毒为模型系统，从基因组到景观尺度研究病毒动力学。口蹄疫病毒是一些进化最快和传染性最强的已知病原体，当它们从野生动物传播到牲畜种群时会造成巨大损失。来自南非克鲁格国家公园的FMDV变异体已被收集和存档超过40年，为评估目前在该公园的布法罗种群中传播的谱系提供了历史和系统发育背景。研究人员将创建一个数据驱动的数学框架，将组织规模上的病毒动力学联系起来，以测试宿主体内的动力学，在人口和景观规模上，是否可以从病毒谱系之间的表型变异中预测。通过实验、观察性实地研究和数学模型，该团队将：发现当前和历史FMDV谱系之间的表型分化模式，评估体外测量的病毒表型性状是否预测活宿主中的病毒动态，探索宿主内病毒和免疫动态如何转化为布法罗群中的FMD动态，确定病毒株之间的变异如何在景观尺度上构建病毒多样性，并鉴定引起家畜暴发的口蹄疫病毒株的基因型和表型。该建模框架将被测试，看看该方法是否正确区分传播，多样化，并在某些情况下溢出到牲畜的历史谱系，从菌株后逐渐消失适度的增长时期。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。