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

今天，我们可以痛苦地认识到，来自动物的传染病对人类生命和社会构成了重大威胁。在我们继续与COVID-19作斗争之际，专家们一致认为，新的流感大流行仍然是一个“何时”而不是“是否”的问题。我们预防和应对未来大流行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。最大的威胁来源是家畜——家禽和猪；全球研究网络已经对这些问题进行了广泛的监测和研究。然而，流行病也可能发生在人们预料不到和不太了解的地方，海豹是一个主要的候选者。我们需要研究海豹的流感有三个原因。首先，灰海豹可能是最大的哺乳动物流感宿主之一，对人类和野生动物都构成威胁。这一点现在尤为重要，因为英国的灰海豹数量正以前所未有的速度增长。其次，与家畜不同，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是如何随着时间的推移适应哺乳动物的。这将增强我们预测未来大流行的来源和性质的能力。第三，有强烈的迹象表明，灰海豹能够与流感共存而不会产生不良影响，而与之密切相关的斑海豹则会遭受大规模死亡事件，其中数千人死亡。对不同海豹物种的比较研究可以揭示这种差异的驱动因素，并为我们提供新的疾病干预措施。在我的研究中，我将使用圣安德鲁斯大学SMRU（海洋哺乳动物研究单位）收集的苏格兰野生灰海豹和斑海豹的拭子和血液样本。我还将使用被送到皇家防止虐待动物协会（RSPCA）和英国政府动植物健康机构（APHA）管理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。在牛津大学，我将使用尖端的测序技术和计算生物学来分析样本，同时在实验室中使用分子方法来研究野生动物生物学。该项目将建立一个全英国范围的合作网络，由来自大学、专业机构、慈善机构和政府机构的合作者组成，以解决与人类和野生动物健康有关的生物学基本问题。

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.