Identifying the genetic mechanisms facilitating host range and virulence of a viral pathogen that threatens European amphibian biodiversity

确定威胁欧洲两栖动物生物多样性的病毒病原体的宿主范围和毒力的遗传机制

基本信息

批准号：
NE/M000338/1
负责人：
Trenton Garner
金额：
$ 35.53万
依托单位：
Zoological Society of London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=NE%2FM000338%2F1
关键词：
Identifying genetic mechanisms facilitating host

项目摘要

Amphibians are experiencing catastrophic declines, caused by the emergence of infectious diseases. In Europe, the causative agent is predominantly viral (ranavirus), and our work has shown that emergence of ranavirus in amphibian communities can result in at least three different patterns: the mortality and population decline can be host-specific, it can affect the whole host community or infections can be asymptomatic, co-occurring in areas where lethal infections are common. From analysis of viral isolates we have determined that this variation correlates with viral phylogeney: in Spain, a genetic lineage responsible for amphibian community mortality and decline co-circulates with a genetically distinct asymptomatic lineage; in the UK, a third lineage is associated with death and decline of a single host species (common frogs - infection of other host species is rare and does not lead to significant mortality or decline in spill-over hosts).Here we propose to take advantage of this novel system to ascertain what genetic factors are responsible for these differences in host range and virulence. Our approach is three-pronged: first, we will sequence 130 ranavirus genomes to catalogue genetic variation amongst the European lineages and identify candidate loci. We will also take a more bottom-up phylogenetic approach, identifying any genetic variants that map with differences in host species in a global panel of ranavirus genomes. Second, we carry out controlled infection experiments to verify the different host range and virulence of different viral isolates in three animal models (two anurans and one caudate chosen to encompass the host range we have observed in Spain). Third, we will generate viral knockouts, targeting candidate regions we have identified in the first two objectives, and test hypotheses regarding gene function using recombinants and wild type virus in our animal models.Our results will be a crucial contribution to our understanding of why ranaviruses are such lethal pathogens in some circumstances. Ranavirus emergence is on the increase across Europe, and is emerging as a novel threat to amphibian and reptile biodiversity in Latin America and Madagascar, two amphibian and reptile biodiversity hotspots. Our research will more widely inform the epidemiological community as to what genetic factors may be important for viruses to exploit novel hosts. Given that most emerging infections are viral and emergence arises through host jumps, we expect our findings to be of broad interest to this community.

两栖动物的出现是由于传染病的出现而导致的灾难性下降。 In Europe, the causative agent is predominantly viral (ranavirus), and our work has shown that emergence of ranavirus in amphibian communities can result in at least three different patterns: the mortality and population decline can be host-specific, it can affect the whole host community or infections can be asymptomatic, co-occurring in areas where lethal infections are common.从对病毒分离株的分析中，我们确定了这种变异与病毒系统差异相关：在西班牙，造成两栖动物社区死亡率的遗传谱系和与遗传上不同无症状的谱系共同循环；在英国，第三个谱系与单个宿主物种的死亡和下降有关（常见青蛙 - 其他宿主物种的感染很少见，并且不会导致溢出宿主的死亡率或下降）。在这里，我们建议利用这一新型系统来确定哪些遗传因素在宿主范围和毒力中造成了这些差异。我们的方法是三个方面的：首先，我们将在欧洲谱系中对130兰纳维病毒基因组进行分类，并确定候选基因座。我们还将采用一种更自下而上的系统发育方法，确定在全球兰纳维病毒基因组中寄主物种差异的任何遗传变异。其次，我们进行了受控的感染实验，以验证三种动物模型中不同病毒分离株的不同宿主范围和毒力（两个动物模型（两种Anurans和一个尾状尾巴）被选为涵盖我们在西班牙观察到的宿主范围）。第三，我们将产生病毒敲除，针对前两个目标中已经确定的候选区域，并在我们的动物模型中使用重组和野生型病毒进行有关基因功能的测试假设。您的结果将是我们对为什么在某些情况下这种兰氏病毒的理解的重要贡献。 Ranavirus的出现在整个欧洲的增长，并且正在成为对拉丁美洲和马达加斯加两栖动物和爬行动物生物多样性热点的新型威胁。我们的研究将更广泛地为流行病学界提供有关哪些遗传因素对病毒开发新宿主可能很重要的信息。鉴于大多数新兴的感染都是病毒，并且通过宿主跳跃而出现，我们希望我们的发现对这个社区具有广泛的兴趣。