The Dynamics of Filovirus Infection in bats in Ghana

这项研究旨在了解在人类中引起致命爆发的高毒力病毒如何在蝙蝠种群中持续存在，而不会在这些动物中造成明显的死亡和疾病。虽然其中一些原因可能与针对特定病毒的免疫系统有关，但其他原因将与宿主这些病毒的蝙蝠的生态和生活方式有关。当这些病毒（包括埃博拉病毒和马尔堡病毒）传播到人群中时，它们会造成大量死亡和疾病，偶尔还会造成重大流行病，如最近的西非埃博拉危机。如果我们了解病毒如何在野生动物宿主中持续存在，我们就可以确定溢出机制，并开发出更好的方法来降低人类爆发的可能性。该计划将检测感染西非加纳蝙蝠的实际埃博拉和马尔堡样病毒（称为丝状病毒），初步测试提供了感染这两种病毒的证据。然后，我们将利用表征数据开发针对加纳病毒的特定测试，而不是使用基于非洲其他地区发现的病毒的测试。这一阶段的工作还将研究埃博拉病毒和马尔堡病毒以及其他丝状病毒在蝙蝠宿主中的变异性，从而为控制它们的策略提供重要信息，例如这些病毒是如何传播的以及医疗干预的有效性。开发的特定检测方法将包括检测病毒基因组的测试，这将能够检测到低水平的特定病毒，以及用于免疫反应的血液测试，以检测先前的感染;一个重要的特点是，这些测试将针对实际感染加纳蝙蝠的丝状病毒的范围进行开发。使用这些测试并与我们在加纳野生动物服务部门的长期兽医合作者合作，我们将在该赠款的2年时间内筛选加纳受感染的蝙蝠栖息地，以了解病毒如何在加纳不同蝙蝠物种之间传播。这将使我们能够区分，例如，埃博拉病毒是否持续在低水平上，持续感染栖息地，或者病毒是否依赖于传播感染波，涉及许多不同的相互关联的蝙蝠栖息地。这种基本知识目前还不存在蝙蝠中的丝状病毒。我们还将使用我们的新检测方法来调查加纳人过去感染的情况，特别是那些与蝙蝠密切接触的人（例如狩猎）。这项工作将通过英国和加纳科学家之间的密切合作来完成，重点是能力建设。剑桥大学有一个主要的能力建设剑桥-非洲方案，其中包括加纳大学作为一个具体的合作伙伴。领导该项目的加纳病毒学家Osbourne Quaye博士受益于该项目的访问奖学金。这项拟议的方案将为他的实验室提供分子和血清学设备，并允许在威斯敏斯特与Wright博士一起开发的专业检测方面进行专门培训。加纳的实地研究将由Richard Suu-Ire博士领导，他最近在加纳大学完成了蝙蝠病毒感染博士学位，由Wood教授和Cunningham教授共同监督。我们还将在我们的加纳合作者与塞拉利昂马克尼大学传染病实验室之间建立南南合作联系。该实验室是在西非埃博拉疫情期间和之后建立的，由Wellcome提供资金，并得到剑桥-非洲计划的支持，以提供基因组学领域的能力。在西非埃博拉疫情期间，UniMak IDRL内的设备被用于提供实时测序能力。

This research aims to understand the enigma of how highly virulent viruses that cause lethal outbreaks in humans can persist in bat populations, without causing obvious death and disease in these animals. While some of the reasons likely relate to immune systems targeting the specific viruses, other reasons will relate to the ecology and lifestyles of the bats that host these viruses. When these viruses, which include Ebola and Marburg, transmit into the human population, they cause significant death and disease and occasional major epidemics, as in the recent West African Ebola crisis. If we understood how the viruses persist in their wildlife reservoir, we could identify mechanisms for spillover and develop better means of reducing the likelihood of outbreaks occurring in humans. The programme will characterise the actual Ebola- and Marburg-like viruses (termed filoviruses) that infect bats in Ghana, West Africa, where preliminary testing has provided evidence of infection with both viruses. Using data from the characterisation, we will then develop specific tests for the viruses in Ghana, rather than using tests based on viruses found in other parts of Africa. This phase of the work will also characterise variability in Ebola and Marburg, and potentially other filoviruses, in their bat hosts, thereby providing important information for strategies to control them, such as how these viruses are transmitted and the effectiveness of medical interventions. The specific assays developed will include tests to detect viral genomes, which will be able to pick-up low levels of specific viruses as well as blood tests for immune responses to detect prior infection; an important feature is that the tests will be developed against the range of filoviruses actually infecting bats in Ghana. Using these tests and working with our long-standing veterinary collaborator in the Ghana wildlife services, we will screen infected bat roosts in Ghana over the 2 year time period of this grant to obtain a picture of how viruses transmit amongst and between different species of bats in Ghana. This will allow us to distinguish whether, for example, Ebola persists at a low level, persistently infecting roosts, or whether the virus depends on spreading waves of infection involving many different interconnected bat roosts. This basic knowledge does not currently exist for filoviruses in bats. We will also use our new tests to investigate the presence of past infection of people in Ghana, in particular in those with livelihoods that bring them in close contact with bats (e.g. hunting). The work will be delivered through careful collaboration between UK-based and Ghanaian scientists, with a strong capacity building focus. Cambridge University has a major capacity building Cambridge-Africa programme that includes the University of Ghana as a specific partner. Dr Osbourne Quaye, the Ghanaian virologist leading the programme there, has benefitted from a visiting fellowship as part of that programme. This proposed programme will fully resource his laboratory with molecular and serological equipment and also allow for specific training in the specialist assays that will be developed with Dr Wright in Westminster. The field studies in Ghana will be led by Dr Richard Suu-Ire, who recently completed his PhD on bat virus infections in the University of Ghana, co-supervised by Professors Wood and Cunningham. We will also establish South-South collaborative links between our Ghanaian collaborators and the University of Makeni Infectious Disease Laboratory (UniMak IDRL), Sierra Leone. This laboratory was established during and following the Ebola epidemic in West Africa with funding from Wellcome and the support of the Cambridge-Africa program to provide capacity in the area of genomics. The equipment within the UniMak IDRL was used during the Ebola epidemic in West Africa to provide real-time sequencing capability.