Advancing genetic tools to understand individual heterogeneity in wildlife-virus interactions

在人类中，年龄在决定我们感染病毒的可能性和患病程度方面发挥着重要作用。研究能够耐受多种病毒感染的长寿动物，可能会给我们提供关于年龄如何影响病毒感染的重要见解。蝙蝠是研究这些问题的理想系统，因为它们的寿命异常长，而且在感染了会导致其他动物严重疾病的病毒时，看起来很健康。然而，方法上的障碍使得很难确定是年长的蝙蝠还是年轻的蝙蝠倾向于更多地感染病毒，以及年龄是否影响它们因这些感染而患病的程度。第一个挑战是，目前在单个蝙蝠体内同时研究所有病毒的成本太高，所以我们必须要么将整个蝙蝠种群的信息归类(丢失单个蝙蝠水平的信息)，要么专注于特定的病毒。不幸的是，这两种方法都提供了关于蝙蝠体内存在的病毒的有偏见的信息。另一个困难是，我们目前确定野生蝙蝠年龄的方法缺乏分辨率，而且往往无法在蝙蝠绝大多数的成年寿命中确定它们的年龄。我们的计划旨在开发技术，利用普通吸血蝙蝠的样本来解决这些困难，吸血蝙蝠是一种蝙蝠物种，以其在美洲狂犬病病毒传播中的重要作用而闻名。我们的项目将首先开发基因工具，以廉价地研究单个蝙蝠体内的所有病毒；这项技术已成功用于细菌，但尚未应用于病毒。接下来，我们将使用最近开发的一种“表观遗传时钟”来确定每只蝙蝠的年龄，这种时钟使用遗传数据从一小片翅膀组织中为蝙蝠设定年龄。然后，我们将把每只蝙蝠体内存在的病毒数据与年龄和其他信息联系起来，以测试蝙蝠之间的个体差异如何影响感染这些动物的病毒的数量和类型。我们的项目将帮助我们了解不同年龄的蝙蝠感染病毒的数量和类型是否会有可预测的不同，这将有助于我们以有利于蝙蝠和人类健康的方式改进对野生蝙蝠的研究和管理。更广泛地说，我们的项目将在我们如何研究动物体内的病毒方面开辟新的前沿，我们开发的技术将有助于在低资源环境下获得这些先进的方法。

In humans, age plays an important role in determining the likelihood we will get infected with a virus and how sick we get. Studying long-lived animals that can tolerate being infected by many viruses is likely to give us important insights into how age influences viral infection. Bats are an ideal system for studying these questions because they have unusually long lifespans and can appear healthy while being infected with viruses which cause severe disease in other animals. However, methodological barriers have made it difficult to determine whether older or younger bats tend to have more viral infections, and whether age influences how sick they get from these infections.A first challenge is that it is currently too expensive to study all viruses at the same time within an individual bat, so we have to either group information from entire bat populations (losing information at the individual bat level) or focus on specific viruses. Unfortunately, both approaches give biased information about the viruses present in bats. Another difficulty is that our current methods for determining the age of wild bats lack resolution, and are often unable to age bats during the vast majority of their adult lifespan. Our proposal aims to develop technologies to resolve these difficulties using samples from common vampire bats, a bat species known for its important role in rabies virus transmission in the Americas.Our project will first develop genetic tools to inexpensively study all the viruses within individual bats; this technique has been successfully used for bacteria but has not yet been applied to viruses. We will next determine the age of each bat, using a recently developed 'epigenetic clock' which uses genetic data to age bats from a small piece of wing tissue. We will then link up the data on viruses present in each bat with age and other information to test how individual differences between bats affect the number and type of viruses which infect these animals. Our project will help us understand whether the number and type of viral infections differs predictably for bats of different ages, which would help us to improve studies and management of wild bats in ways that benefit both bat and human health. More broadly, our project will open new frontiers in how we study viruses in animals, and the technologies we develop will help make these advanced methods accessible in low-resource settings.