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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684008
• 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，密集的水饲养的鱼类，软体动物和甲壳类动物，提出了独特的挑战，与所有其他密集的动物生产系统相比，水生养殖和野生动物出现在同一个水柱中，水生环境参数不能像圈养牲畜农业那样得到非常严格的控制。因此，同一水体中的养殖和野生水生动物都暴露在相同的病毒病原体中，无法实现绝对的生物遏制，因此我们的口号是“一条鱼，一种健康”。对水生病毒的出现、毒力和持久性的病毒遗传特征还没有很好的研究。这项研究计划是关于一种新的鲑鱼冠状病毒，大西洋鲑鱼巴菲尼病毒（ASBV），我们从养殖的大西洋鲑鱼分离。感染鱼类的巢状病毒被分类为冠状病毒科（Coronaviridae）和巢状病毒目（Nidovirales）的巴菲尼病毒属（Bafinivirus）。巢状病毒颗粒被正极性的长单链RNA基因组包被。巴菲尼病毒属的成员主要分离自淡水鲤科物种，例如白色鲷病毒和黑头呆鱼巢状病毒。从加拿大安大略野生大鳞鲑中分离到的大鳞鲑巴菲尼病毒（Chinook salmon bafinivirus，CSBV）是第一个分离到的鲑鱼巴菲尼病毒。虽然CSBV在野生鱼类中的临床意义尚不清楚，但也不确定它将如何威胁养殖鱼类。此外，对巴菲尼病毒生物学的分子研究可能有助于确定巢状病毒进化的主要驱动因素。该研究计划的重点主要是病毒包膜刺突（S）糖蛋白，预计该糖蛋白在该病毒的感染性和免疫原性中起关键作用。这项研究计划的长期目标是从分子水平上详细了解ASBV是如何出现的，以及其确切的发病机制。近期目标是：1）确定这种新病毒的流行及其对鱼类健康的影响; 2）定位ASBV S蛋白S1亚基及其同源宿主细胞表面受体的受体结合结构域，并研究这种病毒的宿主范围潜力; 3）研究ASBV S蛋白在不同鱼类细胞系中复制过程中的引发，并确定其在组织和细胞嗜性、宿主范围和致病性中的作用; 4）研制抗ASBV的疫苗和抗病毒药物。这些研究将有助于我们进一步了解鲑鱼巴菲尼病毒的病毒-细胞和病毒-宿主相互作用的演变。这项研究的结果不仅将对水产养殖业和野生鱼类保护具有重要的实际应用，而且还将具有重要的局部病毒学意义，因为巢状病毒是全球新兴和重新出现的一组病毒，可以突变以扩大其在水生动物、陆生养殖动物、宠物和野生动物以及人类中的宿主范围。