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

水产养殖，即鱼类、软体动物和甲壳类动物的集约化水中养殖，与所有其他集约化动物生产系统相比，具有独特的挑战，因为水生养殖动物和野生动物生活在同一水柱中，并且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，同一水柱中的养殖和野生水生动物都暴露于相同的病毒病原体，无法实现绝对的生物控制，因此我们的口号是“同一鱼，同一健康”。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很好的研究。本研究项目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中分离出来。感染鱼类的尼多病毒属于巴菲尼病毒属、冠状病毒科和尼多病毒目。尼囊病毒颗粒被长单链正极性RNA基因组包裹。巴菲尼病毒属的成员主要是从淡水鲤科动物中分离出来的，例如白鲷鱼病毒和胖头鲦鱼尼病毒。从加拿大安大略省野生奇努克鲑鱼中分离到的奇努克鲑鱼巴菲尼病毒（CSBV）是首次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奈多病毒进化的主要驱动因素。本研究计划的重点主要是病毒包膜刺突(S)糖蛋白，该蛋白被预测在该病毒的传染性和免疫原性中起关键作用。本研究计划的长期目标是获得ASBV如何出现及其确切发病机制的详细分子理解。短期目标是：1)确定这种新型病毒的流行程度及其对鱼类健康的影响；2)定位ASBV S蛋白S1亚基的受体结合域及其同源宿主细胞表面受体，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复制过程中的引物，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)研制ASBV疫苗和抗病毒药物。提出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，因为尼多病毒是一种全球新出现和重新出现的病毒群，它可以变异以扩大其在水生动物、陆地养殖动物、宠物和野生动物以及人类中的宿主范围。

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.