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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615075
• 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 bio­containment 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、软体动物和甲壳类的集约化水产养殖，与所有其他集约化动物生产系统相比，这是一个独特的挑战，因为水产养殖和野生动物出现在同一水柱中，水生环境参数不能像圈养畜牧业那样受到非常严格的控制。因此，养殖和野生水生动物在同一水柱中暴露在相同的病毒病原体下，无法达到绝对的生物遏制，因此我们的口头禅“一条鱼，一条健康”。导致水生病毒出现、毒力和持久性的病毒遗传特征还没有得到很好的研究。本研究是对我们从养殖的大西洋鲑鱼中分离到的一种新的鲑类冠状病毒--大西洋鲑鱼巴菲尼病毒(ASBV)的研究。感染鱼类的Nido病毒被归类为BafiniVirus，冠状病毒科，Nidovirales目。NidVirus颗粒被正极性的长单链RNA基因组所包裹。巴菲尼病毒属的成员主要是从淡水鲤科鱼类中分离出来的，例如白鲍病毒和肥头小鱼尼德病毒。奇努克鲑鱼巴菲尼病毒(CSBV)是从加拿大安大略省野生奇努克鲑鱼中分离到的第一株鲑鱼巴菲尼病毒。虽然CSBV在野生鱼类中的临床意义尚不清楚，但它将如何威胁养殖鱼类还不确定。此外，对BafiniVirus生物学的分子研究可能有助于确定NidoVirus进化的主要驱动因素。这项研究计划的重点主要是病毒包膜尖峰蛋白(S)糖蛋白，预计它在该病毒的传染性和免疫原性中发挥关键作用。这项研究计划的长期目标是从分子上详细了解ASBV是如何产生的，以及它的确切发病机制。近期目标是：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)定位ASBV S蛋白S1亚单位的受体结合域与其同源宿主细胞表面受体(S)，并研究该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的启动，并确定其在组织和细胞嗜性、宿主范围和致病机制中的作用；4)研制针对ASBV的疫苗和抗病毒药物。这些研究将加深我们对鲑鱼巴菲尼病毒病毒-细胞和病毒-宿主相互作用演化的理解。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，而且还将具有重大的局部病毒学兴趣，因为NidoVirus是一组全球新兴和重新出现的病毒，可以变异以扩大其在水生动物、陆地养殖、宠物和野生动物以及人类中的宿主范围。