One Fish, One Health: Biochemistry, infectivity and immunogenicity of a novel salmonid bafinivirus

一条鱼，一种健康：一种新型鲑鱼巴菲尼病毒的生物化学、感染性和免疫原性

• 批准号: RGPIN-2016-04462
• 负责人: Kibenge, Frederick
• 金额: $ 2.26万
• 依托单位: University of Prince Edward Island
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709324
• 关键词: Fish; Health; Biochemistry; infectivity; immunogenicity

Aquaculture, the intensive water rearing of fish, molluscs and crustaceans, presents unique challenges in contrast to all other intensive animal production systems in that the aquatic farmed and wild animals occur in the same water column, and the aquatic environmental parameters cannot be very closely controlled as for captive livestock agriculture. Consequently both farmed and wild aquatic animals in the same water column are exposed to the same viral pathogens, and absolute bio-containment cannot be attained, hence our mantra “One Fish, One Health”. The viral genetic features that account for the emergence, virulence and persistence of aquatic viruses are not well studied. This research program is on a novel salmonid coronavirus, Atlantic salmon bafinivirus (ASBV), we isolated from farmed Atlantic salmon. Nidoviruses that infect fish are classified in the genus Bafinivirus, family Coronaviridae, and order Nidovirales. Nidovirus particles are enveloped with long single-stranded RNA genomes of positive polarity. Members of the genus Bafinivirus have been isolated primarily from freshwater cyprinid species, for example White bream virus and Fathead minnow nidovirus. Chinook salmon bafinivirus (CSBV) from wild Chinook salmon in Ontario, Canada, was the first isolated salmon bafinivirus. While the clinical significance of CSBV in wild fish is unknown, it is uncertain how it would threaten farmed fish. Moreover, molecular studies of the biology of bafiniviruses may help identify major drivers of evolution of nidoviruses. The focus of this research program is primarily on the viral envelope spike (S) glycoprotein, which is predicted to play a key role in the infectivity and immunogenicity of this virus. The long-term goal of this research program is to gain a detailed molecular understanding of how ASBV emerged and its precise mechanisms of pathogenesis. The short-term objectives are:1) determine the prevalence of this novel virus and its impact on fish health; 2) map the receptor-binding domain in the S1 subunit of the ASBV S protein and its cognate host cell surface receptor(s) and investigate the host range potential of this virus; 3) study the ASBV S protein priming during replication in different fish cell lines and establish its role in tissue and cell tropism, host range and pathogenesis; 4) develop vaccines and antiviral drugs against ASBV. The proposed studies will advance our understanding of the evolution of virus-cell and virus-host interactions of Salmon bafinivirus. The outcomes of this research will not only have important practical applications for the aquaculture industry and for wild fish conservation, but will also be of significant topical virological interest since nidoviruses are a globally emerging and re-emerging group of viruses that can mutate to extend their host range in aquatic animals, and in terrestrial farmed, pet, and wild - animals, and in humans.

水产养殖，鱼，软体动物和甲壳类动物的密集水饲养，与所有其他密集的动物生产系统相比，水生野生动物和野生动物出现在同一水柱中，而水生环境参数则不能得到非常封闭的控制，因为圈养的牲畜农业不能得到非常近的控制。因此，同一水柱中的野生水产动物和野生水产动物都暴露于相同的病毒病原体，绝对的生物含量不能附着，因此我们的咒语“一条鱼，一种健康”。研究了水生病毒的出现，病毒和持久性的病毒遗传特征尚未得到很好的研究。该研究计划是在一种新型的鲑鱼冠状病毒，大西洋鲑鱼bafinivivirus（ASBV）上，我们从养殖的大西洋鲑鱼中分离出来。感染了被感染鱼类的Nidovires分类为Bafinivivirus属，冠状病毒家族和命令Nidovirales。 Nidovirals。 nidovirus颗粒被阳性极性的长单链RNA基因组笼罩。 Bafinivivivulus属的成员已从淡水Cyprinid物种中分离出来，例如白色胸罩病毒和Fathead Minnow nidovirus。来自加拿大安大略省野生奇努克鲑鱼的奇努克鲑鱼巴菲病病毒（CSBV）是第一个孤立的鲑鱼bafinivivirus。尽管CSBV在野生鱼类中的临床意义尚不清楚，但尚不确定它将如何威胁养殖鱼类。此外，对Bafiniviruses生物学的分子研究可能有助于鉴定Nidovires进化的主要驱动因素。该研究计划的重点主要放在病毒包膜尖峰（S）糖蛋白上，该糖蛋白预测在该病毒的感染和免疫原性中起关键作用。该研究计划的长期目标是对ASBV的出现及其发病机理的精确机制获得详细的分子理解。短期目标是：1）确定这种新型病毒的流行及其对鱼类健康的影响； 2）绘制ASBV S蛋白S1亚基中的受体结合结构域及其同源宿主细胞表面受体（S），并研究该病毒的宿主范围电位； 3）研究在不同鱼类细胞系中复制过程中的ASBV S蛋白启动，并在组织和细胞向量，宿主范围和发病机理中确立其作用； 4）开发针对ASBV的疫苗和抗病毒药物。拟议的研究将促进我们对鲑鱼巴菲病毒病毒细胞和病毒宿主相互作用的演变的理解。这项研究的结果不仅将在水产养殖行业和野生鱼类保护方面具有重要的实际应用，而且还将具有重大的局部病毒学兴趣，因为Nidovires是一种全球的新兴和重新出现。可以突变以扩展其在水生动物以及陆生养殖，宠物和野生动物以及人类中的一组病毒。