Canadian bats and their viruses: From benevolent relationships to spillover to other species

有几种病毒在它们的天然宿主蝙蝠中似乎不会引起明显的疾病，但它们已经蔓延到其他哺乳动物身上，造成严重的、往往是致命的疾病。这些病毒包括引起严重急性呼吸系统综合症（SARS）、中东呼吸综合征（MERS）的病毒；马尔堡和埃博拉出血病；亨德拉和尼帕呼吸和神经系统疾病，以及猪流行性腹泻。虽然有许多关于这些病毒与其外溢宿主或替代实验动物的相互作用的研究，但关于这些病毒或类似病毒与其天然蝙蝠宿主的关系的信息很少。因此，我们不知道这些病毒和它们的蝙蝠宿主在它们向相对良性关系的共同进化过程中经历了哪些适应。关于环境和其他因素如何改变蝙蝠-病毒的良性关系，从而导致溢出到其他物种的信息也很少。为了填补这些重要的知识空白，我们实验室的长期目标是确定两种常见的加拿大蝙蝠和它们的病毒之间的关系，以及破坏这种通常良性关系导致病毒复制增加的因素。虽然已经研究了亨尼帕病毒在其食果蝙蝠宿主中的相互作用，但我们的工作是唯一已知的在食虫蝙蝠中检验自然病毒与宿主关系的尝试。我们已经确定并鉴定了一种独特的冠状病毒（与SARS， MERS和PED引起的病毒有关）和一种自然感染两种加拿大蝙蝠的疱疹病毒。许多（如果不是大多数的话）蝙蝠似乎持续感染了这些病毒，病毒复制有限，没有明显的病理或疾病迹象。我们的初步研究表明，致命真菌的继发性感染会导致蝙蝠病毒载量的大幅增加，可能导致溢出。我们定义蝙蝠-病毒关系的策略将是利用蝙蝠基因表达的广泛而深入的信息，形成蝙蝠如何对真菌和病毒感染作出反应的假设，在细胞培养模型中测试这些假设，然后在与蝙蝠生物学家的合作研究中，在实地样本中验证结果。我们的研究不仅将提供这些特殊哺乳动物中病毒与宿主关系的基本信息，而且还将提供线索，以减轻通常伴随病毒从蝙蝠扩散到人类和其他物种的严重后果。

Several viruses, that appear to cause no overt illness in their natural bat hosts, have spilled over into other mammals causing serious and often fatal disease. These include viruses that cause Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS); Marburg and Ebola haemorrhagic disease; Hendra, and Nipah respiratory and neurological disease, and porcine epidemic diarrhea (PED). While there are many studies on the interaction of these viruses with their spillover hosts or surrogate laboratory animals, there is little information on the relationship of these or similar viruses with their natural bat hosts. We therefore do not know the adaptations these viruses and their bat hosts have undergone during their co-evolution towards relatively benign relationships. There is also little information on how environmental and other factors alter the benign bat-virus relationship leading to spillover to other species. To fill these important knowledge gaps, the long-term goal of our laboratory is to define the relationship between two species of common Canadian bats and their viruses, and factors that disrupt this normally benign relationship leading to increased virus replication. Although interactions between Henipah viruses in their fruit-eating bat hosts have been studied, our work is the only known attempt to examine natural virus-host relationships in insectivorous bats. We have identified and characterized a unique coronavirus (related to SARS, MERS and PED causing viruses) and a herpes virus that naturally infect two Canadian bat species. Many, if not most bats, appear to be persistently infected with these viruses with limited virus replication and no overt signs of pathology or illness. Our preliminary studies suggest that secondary infection with a lethal fungus causes a large increase in virus load in the bats, potentially leading to spillover. Our strategy to define bat-virus relationships will be to use broad and deep information on gene expression in bats to form hypotheses on how bats respond to fungal and viral infection, test these hypotheses in cell culture models and then, in collaborative studies with bat biologists, validate the results in field samples. Our studies will not only provide fundamental information about virus-host relationships in these specialized mammals, but will also give clues about mitigating the serious consequences that often accompany viral spillover from bats to humans and other species.