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实质性威胁。在我们继续应对新冠肺炎疫情之际，专家们一致认为，新一轮流感大流行仍然是一个“何时”的问题，而不是“如果”的问题。我们预防和应对未来大流行的能力取决于识别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它们进行了广泛的监测和研究。然而，疫情也可能发生在预期和了解较少的地方，而海豹是主要的候选对象。我们需要研究海豹体内的流感有三个原因。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，这种流感对人类和野生动物都构成了威胁。这一点现在尤其重要，因为英国灰海豹的数量增长达到了前所未有的水平。其次，与家畜不同，流感在野生灰海豹种群中自由传播，无需任何人类干预。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。这将增强我们总体上预测未来大流行的源头和性质的能力。第三，有强烈的迹象表明，灰海豹设法与流感共存，没有不良影响，而与之密切相关的海豹已知会遭受大规模死亡事件，数千人死亡。对不同种类海豹的比较研究可以揭示这种差异的驱动因素，并引导我们进行新的疾病干预。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海豹的拭子和血液样本。我还将使用被带到由皇家防止虐待动物协会(RSPCA)和英国政府动植物卫生局(APHA)运营的野生动物救援中心的搁浅海豹的样本。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，我将用尖端的测序技术和计算生物学分析样品，并在实验室里用分子方法研究野生动物生物学。该项目将在英国范围内建立一个由大学、专业机构、慈善机构和政府机构的合作者组成的网络，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.