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以及我们生病的程度方面起着重要作用。研究能够忍受多种病毒感染的长寿动物可能会让我们对年龄如何影响病毒感染有重要的见解。蝙蝠是研究这些问题的理想系统，因为它们的寿命非常长，并且在感染病毒时可以表现出健康，而这些病毒会在其他动物中引起严重疾病。然而，方法上的障碍使得很难确定老年蝙蝠或年轻蝙蝠是否倾向于有更多的病毒感染，以及年龄是否会影响它们从这些感染中获得的疾病程度。第一个挑战是，目前在单个蝙蝠中同时研究所有病毒过于昂贵，因此，我们必须要么将整个蝙蝠种群的信息分组（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，这两种方法都给出了关于蝙蝠中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，并且通常无法在蝙蝠成年寿命的绝大多数时间内对其进行老化。我们的提案旨在开发技术，以解决这些困难，使用普通吸血蝙蝠的样本，这是一种蝙蝠物种，在美洲的狂犬病病毒传播中起着重要作用。我们的项目将首先开发基因工具，以廉价的方式研究单个蝙蝠体内的所有病毒。该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“表观遗传时钟”来确定每只蝙蝠的年龄，该时钟使用遗传数据从一小块翅膀组织中确定蝙蝠的年龄。然后，我们将把每只蝙蝠身上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病毒感染的数量和类型是否存在可预测的差异，这将有助于我们以有利于蝙蝠和人类健康的方式改善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病毒方面开辟新的领域，我们开发的技术将有助于使这些先进的方法在低资源环境中可用。

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.