Integrating metavBB/Y006879/1iromics with epidemiological dynamics: understanding rodent virus transmission in the Anthropocene

大多数影响人类的新发传染病，包括艾滋病、流感和COVID-19，都是由源自非人类动物的RNA病毒引起的。近年来，这种“人畜共患”病毒性疾病变得更加常见和广泛，这种模式通常归因于日益加剧的环境变化。值得注意的是，不断升级的人类活动通过将自然景观转变为农业农田和城市环境，破坏和扰乱了野生动物的栖息地。结果，我们极大地改变了野生动物群落和病毒在这些群落中的传播方式，同时通过消除分离物种的历史生态屏障，增加了我们接触新的动物病毒的机会。环境的时间变化，如季节变化或气候变化，也可改变野生动物种群中的病原体流行率并影响人畜共患病风险。尽管对病毒性人畜共患病进行了大量研究，但对病毒溢出风险的可操作的、现实世界的预测仍然难以捉摸。预防和控制未来病毒性人畜共患病的一个关键障碍是缺乏关于环境的物理和时间差异如何影响野生动物种群中的病毒传播以及病毒传播和群落组成的变化如何转化为人类风险的基本知识。对动物宿主内人畜共患病动态的预测性理解是预测出现或设计预防出现的干预措施的先决条件。然而，在研究野生动物中的高风险病毒方面的财政和后勤挑战——从需要对个体进行定期监测到所涉及的昂贵的生物安全预防措施——目前阻碍了大多数野生动物疾病系统的这种理解。我们将通过关注野生啮齿动物来应对这些挑战，野生啮齿动物是全球重要的病毒宿主，比任何其他哺乳动物都要负责更多的人畜共患疾病，并且代表了经过充分研究和可处理的系统，可以了解环境对人畜共患病毒传播的影响。许多啮齿动物生活在人类附近，对环境变化的反应非常敏感，无论是在种群动态方面，还是通过增加与人类接触的行为变化。然而，尽管有这些间接证据，驱动病毒在野生啮齿动物种群中传播的潜在生态机制仍然是假设的，重要的是，还远远不能预测。该项目将利用在英国和乌干达建立的实地研究来调查病毒如何在野生啮齿动物中传播，该研究监测野生啮齿动物群落的时间和空间：1)为了解决研究病毒传播的实际挑战，我们将开发新的工具，从越来越容易获得和低成本的宿主病毒数据中推断流行病学动态和人畜共患病风险。这种灵活的方法将允许从横截面样本中进行流行病学推断，并指导适当的采样策略，以便在新的宿主系统中解释元病毒学数据，从而快速发现和监测人畜共患病毒。2)通过在英国牛津郡进行的长期捕获-标记-再捕获野生动物研究，我们将确定季节性环境变化如何影响啮齿动物病毒群落。3)我们将在乌干达沿着土地覆盖梯度使用实地站点，以了解物理环境变化如何影响啮齿动物群落人畜共患病的风险。具体而言，我们将确定人畜共患病危害的本地和景观驱动因素，以及人类如何改变行为以影响这一梯度上的人畜共患病风险。总之，这项研究将大大提高我们对关键宿主体内病毒病原体的理解，并确定增加人畜共患病风险的重要环境驱动因素。

Most emerging infectious diseases affecting humans, including AIDS, influenza, and COVID-19, are caused by RNA viruses originating from non-human animals. In recent years, such 'zoonotic' viral diseases have become more common and widespread, a pattern frequently attributed to increasing environmental change. Notably, escalating human activity has destroyed and disrupted wild animal habitats by converting natural landscapes into agricultural farmlands and urban environments. As a result, we have drastically altered wild animal communities and how viruses circulate within these communities while simultaneously increasing our exposure to new animal viruses by eliminating historical ecological barriers separating species. Temporal changes in the environment, such as seasonal variation or climate change, can also alter pathogen prevalence in wild animal populations and influence zoonotic risk. Despite significant research on viral zoonoses, actionable, real-world predictions of virus spillover risk remain elusive. A critical barrier to preventing and controlling future viral zoonoses is a lack of basic knowledge about how physical and temporal differences in the environment impact virus transmission within wild animal populations and how changes in viral transmission and community composition translate to human risk. Attaining a predictive understanding of the dynamics of zoonoses within their animal reservoirs is a precondition to anticipate emergence or devise interventions that prevent emergence. However, financial and logistical challenges in studying high-risk viruses in wild animals - from the need for regular monitoring of individuals to the costly biosafety precautions involved - currently impede such understanding in most wildlife disease systems. We will address these challenges by focusing on wild rodents, which are important viral reservoirs globally, responsible for more zoonoses than any other mammalian order, and represent well-studied and tractable systems for understanding the environmental impact on zoonotic virus transmission. Many rodents live in close proximity to human populations and are highly responsive to environmental change, both in their population dynamics and via behavioural changes that increase contact with humans. However, despite this circumstantial evidence, the underlying ecological mechanisms driving virus transmission within wild rodent populations remain hypothetical and, importantly, are far from predictive. This project will investigate how viruses circulate in wild rodents using established field studies in England and Uganda, which monitor wild rodent communities over time and space: 1) To tackle the practical challenges of studying viral transmission, we will develop new tools to infer epidemiological dynamics and zoonotic risk from increasingly accessible and low-cost host virome data. This flexible approach will allow rapid discovery and monitoring of zoonotic viruses by enabling epidemiological inferences from cross-sectional samples and guidance for appropriate sampling strategies to interpret metaviromic data in new host systems. 2) Using a long-term capture-mark-recapture wild study in Oxfordshire, UK, we will determine how seasonal environmental change influences rodent viral communities. 3) We will use field sites along a gradient of land cover in Uganda to understand how physical environmental change influences the risk of zoonotics in rodent communities. Specifically, we will identify local and landscape drivers of zoonotic hazards and how humans change behaviour to affect zoonotic risk across this gradient. Together, this research will substantially improve our understanding of viral pathogens within key reservoir hosts and identify important environmental drivers that increase zoonotic risk.