Wild-caught bats as a model to understand the evolution of virus-host interactions

蝙蝠作为传粉者和昆虫控制者，在生态上具有重要意义。它们也被认为是几种新出现和重新出现的病毒的天然宿主，这些病毒是重要的人类和农业感染的病原体。据推测，这些病毒直接或通过中间宿主从蝙蝠身上溢出或“跳过”到人类和其他动物身上，导致严重的、往往是致命的疾病。尽管有证据表明蝙蝠携带多达数百种这样的病毒，但它们似乎没有表现出明显的症状或临床感染迹象。为什么蝙蝠对这些病毒感染不是完全允许的，以及允许它们成为这些病毒的携带者或储藏者的生理特征，人们几乎什么都不知道。因此，蝙蝠为研究病毒生态和病毒-宿主进化提供了一个有趣且相关的模型系统。通过了解蝙蝠如何控制与病毒感染相关的病理，我们可以获得对病毒宿主进化的重要见解，并利用这些知识构建替代抗病毒疗法，特别是针对与大流行有关的新出现的病毒。这项探索基金的目标是利用Mossman博士(病毒与宿主的相互作用和先天免疫)、Banerjee博士(病毒和蝙蝠宿主反应)和Faure博士(蝙蝠生理学)的专业知识，与世界上唯一一个包含野生捕获和繁殖动物的蝙蝠群体(麦克马斯特蝙蝠实验室)，产生一个独特的创新计划。我们建议开发细胞系和工具，用来研究病毒蝙蝠相互作用的机制。特别是，我们将专注于宿主干扰素反应的特定成分，这是哺乳动物的主要抗病毒反应，我们有初步数据表明，蝙蝠的反应与人类的反应显著不同。我们将进一步开发一个使用加拿大大棕色蝙蝠的体内模型系统，以研究病毒感染以及随后蝙蝠的内在和先天反应。由于病毒感染会改变寄主过程，如繁殖、生长和发育，了解病毒与蝙蝠相互作用的动态是很重要的，因为蝙蝠发挥着重要的生态作用。此外，了解蝙蝠是如何藏匿和传播病毒的，对动物和人类的疾病控制具有重要意义。由于大型棕色蝙蝠自然出现在加拿大，我们的发现将直接影响加拿大的农业和卫生部门。此外，这些发现将为疾病控制和新型抗病毒疗法的开发提供全球战略，特别是针对蝙蝠似乎携带的新出现的病毒。最后，该计划将为在多学科环境中培养高素质人才奠定基础。

Bats are ecologically important as pollinators and insect controllers. They are also considered to be natural reservoirs for several emerging and re-emerging viruses that are causative agents of important human and agricultural infections. These viruses are speculated to have spilled over or “jumped” from bats to humans and other animals, directly or through intermediate hosts, causing severe and often fatal disease. Despite evidence of bats harboring up to hundreds of these viruses, they do not appear to show overt symptoms or clinical signs of infection. Little to nothing is understood why bats are not fully permissive to these viral infections and the physiological characteristics that allow them to be carriers or reservoirs of these viruses. Thus, bats provide an intriguing and relevant model system with which to study virus ecology and virus-host evolution. By understanding how bats control the pathology associated with virus infection, we can gain important insights into virus-host evolution, and leverage this knowledge for the construction of alternative anti-viral therapies, particularly for newly emerging virus that are linked with pandemics. This goal of this Discovery Grant is to generate a unique and innovative program that leverages the expertise of Dr. Mossman (virus-host interactions and innate immunity), Mr. Banerjee (viruses and bat host responses) and Dr. Faure (bat physiology) with the world's only bat colony containing wild caught and bred animals (McMaster Bat Lab). We propose to develop cell lines and tools with which to study mechanisms of virus bat interactions. In particular, we will focus on specific components of the host interferon response, the primary anti-viral response of mammals, for which we have preliminary data suggesting the response in bats differs significantly from that in humans. We will further develop an in vivo model system using Canadian big brown bats to study virus infection and subsequent intrinsic and innate responses in bats. As viral infections can alter host processes such as breeding, growth and development, it is important to understand dynamics of virus-bat interactions, as bats serve an important ecological role. Further, understanding how bats harbor and spread viruses has implications for disease control in animals and humans. As big brown bats naturally occur in Canada, our findings will directly impact the Canadian agricultural and health sectors. Moreover, findings will inform global strategies for disease control and development of novel antiviral therapies, particularly for new emerging viruses that bats appear to carry. Finally, this program will form the foundation for training of highly qualified personnel in a multidisciplinary environment.