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

• 批准号: NE/M00080X/1
• 负责人: Richard Nichols
• 金额: $ 7.26万
• 依托单位: Queen Mary University 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%2FM00080X%2F1
• 关键词: Identifying; genetic; mechanisms; facilitating; host

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.

由于传染病的出现，两栖动物正在经历灾难性的衰退。在欧洲，病原体主要是病毒（蛙病毒），我们的工作表明，两栖动物群落中蛙病毒的出现可以导致至少三种不同的模式：死亡率和种群数量下降可能是宿主特异性的，它可以影响整个物种。宿主社区或感染可能是无症状的，在致命感染常见的地区同时发生。通过对病毒分离株的分析，我们确定这种变异与病毒系统发育相关：在西班牙，导致两栖动物群落死亡和衰退的遗传谱系与遗传上不同的无症状谱系共同循环；在英国，第三种谱系与单一宿主物种的死亡和衰退有关（普通青蛙 - 其他宿主物种的感染很少见，并且不会导致溢出宿主的显着死亡或下降）。在这里，我们建议采取利用这个新系统来确定哪些遗传因素导致了宿主范围和毒力的这些差异。我们的方法是三管齐下的：首先，我们将对 130 个蛙病毒基因组进行测序，以对欧洲谱系中的遗传变异进行分类并确定候选基因座。我们还将采取更加自下而上的系统发育方法，识别与全球蛙病毒基因组中宿主物种差异相对应的任何遗传变异。其次，我们进行了受控感染实验，以验证三种动物模型（选择两种无尾动物和一种尾状动物来涵盖我们在西班牙观察到的宿主范围）中不同病毒分离株的不同宿主范围和毒力。第三，我们将产生病毒敲除，针对我们在前两个目标中确定的候选区域，并在我们的动物模型中使用重组病毒和野生型病毒测试有关基因功能的假设。我们的结果将为我们理解蛙病毒的原因做出重要贡献在某些情况下是致命的病原体。整个欧洲蛙病毒的出现正在增加，并且正在成为拉丁美洲和马达加斯加这两个两栖动物和爬行动物生物多样性热点地区两栖动物和爬行动物生物多样性的新威胁。我们的研究将更广泛地告知流行病学界哪些遗传因素对于病毒利用新宿主可能很重要。鉴于大多数新出现的感染都是病毒性的，并且是通过宿主跳跃而出现的，我们希望我们的发现能够引起该社区的广泛兴趣。

项目成果

Temperature is a key driver of a wildlife epidemic and future warming will increase impacts

温度是野生动物流行的关键驱动因素，未来变暖将加剧影响

• DOI: http://dx.10.1101/272369
• 发表时间: 2018
• 作者: Price S

DETECTION AND REPORTING OF RANAVIRUS IN AMPHIBIANS: EVALUATION OF THE ROLES OF THE WORLD ORGANISATION FOR ANIMAL HEALTH AND THE PUBLISHED LITERATURE.

两栖动物中雷诺病毒的检测和报告：对世界动物卫生组织和出版文献的作用的评估。

• DOI: http://dx.10.7589/2016-08-176
• 发表时间: 2017
• 期刊: Journal of wildlife diseases
• 影响因子: 1.3
• 作者: Black Y

A de novo Assembly of the Common Frog (Rana temporaria) Transcriptome and Comparison of Transcription Following Exposure to Ranavirus and Batrachochytrium dendrobatidis.

普通青蛙（Rana temporaria）转录组的从头组装以及暴露于蛙病毒和 Batrachochytrium dendrobatidis 后的转录比较。

• DOI: http://dx.10.1371/journal.pone.0130500
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Price SJ

Outbreaks of an Emerging Viral Disease Covary With Differences in the Composition of the Skin Microbiome of a Wild United Kingdom Amphibian

一种新出现的病毒性疾病的爆发与英国野生两栖动物皮肤微生物组的组成存在差异

• DOI: http://dx.10.3389/fmicb.2019.01245
• 发表时间: 2019
• 期刊: Frontiers in Microbiology
• 影响因子: 5.2
• 作者: Campbell L

Diversity-Stability Dynamics of the Amphibian Skin Microbiome and Susceptibility to a Lethal Viral Pathogen

两栖动物皮肤微生物群的多样性稳定性动态和对致命病毒病原体的易感性

• DOI: http://dx.10.3389/fmicb.2019.02883
• 发表时间: 2019
• 期刊: Frontiers in Microbiology
• 影响因子: 5.2
• 作者: Harrison X