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

大多数影响人类的新出现的传染病，包括艾滋病、流感和新冠肺炎，都是由源自非人类动物的核糖核酸病毒引起的。近年来，这种人畜共患的病毒性疾病变得更加常见和普遍，这种模式往往被归因于日益严重的环境变化。值得注意的是，不断升级的人类活动破坏和扰乱了野生动物的栖息地，将自然景观转变为农业农田和城市环境。结果，我们彻底改变了野生动物群落以及病毒在这些群落内传播的方式，同时通过消除分隔物种的历史生态屏障，增加了我们对新动物病毒的暴露。环境的时间变化，如季节变化或气候变化，也可以改变野生动物种群中病原体的流行率，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、真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。对动物宿主内的人畜共患病的动态进行预测性了解，是预测出现或制定预防出现的干预措施的先决条件。然而，研究野生动物高危病毒的财务和后勤挑战--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目导致更多的人畜共患病，并代表着经过充分研究和处理的系统，用于了解环境对人畜共患病病毒传播的影响。许多啮齿动物生活在人类种群附近，对环境变化高度敏感，无论是在它们的种群动态中，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，推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，更重要的是，远不能预测。该项目将利用英格兰和乌干达现有的现场研究来调查病毒如何在野生啮齿动物中传播，这些研究在时间和空间上监测野生啮齿动物群落：1)为了应对研究病毒传播的实际挑战，我们将开发新的工具，从越来越容易获得的低成本宿主病毒数据中推断流行病学动态和人畜共患病风险。这一灵活的方法将使人畜共患病病毒能够通过横断面样本的流行病学推断和指导适当的抽样战略来快速发现和监测，以便在新的宿主系统中解释后生生物数据。2)利用在英国牛津郡进行的一项长期捕获-标记-再捕获野生研究，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)我们将使用乌干达土地覆盖梯度上的实地考察，以了解自然环境变化如何影响啮齿动物群落中人畜共患病的风险。具体地说，我们将确定人畜共患病危害的当地和景观驱动因素，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。总而言之，这项研究将大大提高我们对关键宿主内病毒病原体的了解，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.