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具有重要的生态学意义。它们还被认为是几种新出现和再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，这些病毒是直接或通过中间宿主从蝙蝠溢出或“跳跃”到人类和其他动物身上，造成严重且往往致命的疾病。尽管有证据表明蝙蝠携带多达数百种这种病毒，但它们似乎没有表现出明显的感染症状或临床症状。人们几乎不知道为什么蝙蝠不能完全接受这些病毒感染，也不知道蝙蝠的生理特征使它们成为这些病毒的携带者或宿主。因此，蝙蝠为研究病毒生态学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，我们可以获得有关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，特别是与大流行相关的新出现病毒。******这个发现基金的目标是产生一个独特的创新计划，利用莫斯曼博士（病毒-宿主相互作用和先天免疫），班纳吉先生（病毒和蝙蝠宿主反应）和福尔博士（蝙蝠生理学）的专业知识，与世界上唯一的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）。我们建议开发细胞系和工具来研究病毒与蝙蝠相互作用的机制。特别是，我们将重点关注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有很大不同。我们将进一步开发一个体内模型系统，使用加拿大大棕蝙蝠来研究病毒感染及其随后的内在和先天反应。由于病毒感染可以改变宿主的繁殖、生长和发育过程，因此了解病毒与蝙蝠相互作用的动力学非常重要，因为蝙蝠在生态中起着重要的作用。此外，了解蝙蝠如何藏匿和传播病毒对动物和人类的疾病控制具有重要意义。由于大棕色蝙蝠自然存在于加拿大，我们的研究结果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开发新的抗病毒疗法的全球战略提供信息，特别是针对蝙蝠似乎携带的新出现的病毒。最后，该计划将形成在多学科环境中培养高素质人才的基础

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.**