Seals: a natural experiment in cross-species transmission, adaptation and pathogenicity of influenza A virus

海豹：甲型流感病毒跨物种传播、适应和致病性的自然实验

• 批准号: BB/W009404/1
• 负责人: Divya Venkatesh
• 金额: $ 51.64万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW009404%2F1
• 关键词: Seals; natural; experiment; cross; species

Today, we can painfully appreciate that infectious diseases from animals pose a substantial threat to human life and society. As we continue to grapple with COVID-19, experts agree that a new influenza pandemic remains a matter of 'when', not 'if'. Our ability to prevent and respond to future pandemics depends on identifying all potential sources of influenza that could spill over into humans and designing new treatments and vaccines. The biggest source of threat are livestock - poultry and pigs; these are extensively monitored and studied by global research networks already. However, an epidemic can also arise from a less expected and understood place, and seals are a prime candidate. There are three reasons why we need to study influenza in seals. First, grey seals are likely one of the largest least well-understood mammalian reservoirs of influenza, which pose a threat to both humans and wildlife. This is especially important now because grey seals in the UK are seeing an unprecedented level of population growth. Second, unlike livestock, influenza spreads freely in wild populations of grey seals without any human intervention. This offers a unique natural experiment, from which we can learn how influenza adapts to mammals over time. This will enhance our ability to predict the source and nature of future pandemics generally. Third, there are strong indications that grey seals manage to co-exist with influenza without adverse effects, while closely related harbour seals are known to suffer mass mortality events where thousands die. A comparative study of the different seal species can uncover drivers of the difference and lead us to new disease interventions. In my study, I will use swab and blood samples from wild grey and harbour seals in Scotland collected by SMRU (Sea Mammal Research Unit) at the University of St Andrews. I will also use samples from stranded seals taken to wildlife rescue centres run by the RSPCA (Royal Society for Prevention of Cruelty to Animals) and the UK government's APHA (Animal and Plant Health Agency). My aims are to understand the dynamics of influenza infections in seal populations and to identify the host factors that drive differences in disease severity. At Oxford, I will analyse the samples with cutting-edge sequencing technologies and computational biology, along with molecular methods to study wild animal biology in the lab. The project will establish a UK-wide network of collaborators from universities, specialist institutions, charities, and government agencies to address fundamental questions in biology with implications for human and wildlife health.

今天，我们可以痛苦地认识到，来自动物的传染病对人类生活和社会构成了重大威胁。随着我们继续与COVID-19作斗争，专家们一致认为，新的流感大流行仍然是一个“何时”而不是“如果”的问题。我们预防和应对未来大流行病的能力取决于确定可能蔓延到人类的所有潜在流感来源，并设计新的治疗方法和疫苗。最大的威胁来源是牲畜、家禽和猪;全球研究网络已经对这些进行了广泛的监测和研究。然而，流行病也可能来自一个不太预期和理解的地方，海豹是一个主要的候选人。我们需要研究海豹流感有三个原因。首先，灰海豹可能是最大的最不为人所知的哺乳动物流感宿主之一，对人类和野生动物都构成威胁。这一点现在尤其重要，因为英国的灰海豹数量增长达到了前所未有的水平。其次，与牲畜不同，流感在野生灰海豹种群中自由传播，无需任何人为干预。这提供了一个独特的自然实验，从中我们可以了解流感如何随着时间的推移适应哺乳动物。这将提高我们预测未来大流行病的来源和性质的能力。第三，有强烈的迹象表明，灰海豹设法与流感共存而没有不利影响，而密切相关的斑海豹则被称为遭受大规模死亡事件，数千人死亡。对不同海豹物种的比较研究可以揭示差异的驱动因素，并引导我们采取新的疾病干预措施。在我的研究中，我将使用拭子和血液样本从野生灰海豹和斑海豹在苏格兰收集的SMRU（海洋哺乳动物研究单位）在圣安德鲁斯大学。我还将使用被带到RSPCA（皇家防止虐待动物协会）和英国政府动植物卫生署（APHA）运营的野生动物救援中心的搁浅海豹样本。我的目标是了解海豹种群中流感感染的动态，并确定导致疾病严重程度差异的宿主因素。在牛津，我将用尖端的测序技术和计算生物学分析样本，沿着分子方法在实验室研究野生动物生物学。该项目将建立一个由来自大学、专业机构、慈善机构和政府机构的合作者组成的全英国网络，以解决生物学中对人类和野生动物健康有影响的基本问题。