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.

水产养殖是鱼类、软体动物和甲壳类动物的集约化水体养殖，与所有其他集约化动物生产系统相比，面临着独特的挑战，因为水生养殖和野生动物发生在同一水体中，并且水生环境参数无法非常严格地控制对于圈养畜牧业，我们检查了同一水体中的养殖和野生水生动物接触相同的病毒病原体，无法实现绝对的生物遏制，因此我们的口号是“一条鱼，一个健康”。导致水生病毒出现、毒力和持久性的病毒遗传特征尚未得到充分研究，该研究项目是针对一种新型鲑鱼冠状病毒，即大西洋鲑鱼巴菲尼病毒（ASBV），我们从感染鱼类的养殖大西洋鲑鱼中分离出这种病毒。属于巢状病毒目、冠状病毒科的巴菲尼病毒属，颗粒被正极性的长单链RNA基因组包裹。巴菲尼病毒主要从淡水鲤鱼物种中分离出来，例如来自加拿大安大略省野生奇努克鲑鱼的白鳊病毒和黑头鲑鱼尼多病毒（CSBV），是第一个在野生中分离的鲑鱼巴菲尼病毒。由于对鱼类的影响尚不清楚，因此不确定它如何威胁养殖鱼类。此外，对bafiniviruses生物学的分子研究可能有助于确定nidoviruses进化的主要驱动因素。该研究项目的重点主要集中在病毒包膜刺突（S）糖蛋白上，预计该蛋白在该病毒的感染性和免疫原性中发挥关键作用。该研究项目的长期目标是获得详细的分子了解。短期目标是：1) 确定这种新型病毒的流行情况及其对鱼类健康的影响；2) 绘制 ASBV S 的 S1 亚基的受体结合域图谱。蛋白质及其同源物宿主细胞表面受体并研究该病毒的宿主范围潜力；3) 研究不同鱼类细胞系中复制过程中的 ASBV S 蛋白启动，并确定其在组织和细胞趋向性、宿主范围和发病机制中的作用 4) 开发；拟议的研究将促进我们对鲑鱼巴菲尼病毒的病毒-细胞和病毒-宿主相互作用的进化的理解，这项研究的成果不仅对水产养殖业和野生鱼类具有重要的实际应用。保护，但也将具有重要的主题病毒学意义，因为巢病毒是全球范围内不断出现和重新出现的病毒组，它们可以发生突变以扩大其在水生动物、陆生养殖、宠物和野生动物以及动物中的宿主范围。人类。