PDF(Pubmed)
Abstract：
Spring viremia of carp virus (SVCV) has a broad fish host spectrum and is responsible for a disease that generally affects juvenile fishes with a mortality rate of up to 90%. In the absence of treatments or vaccines against SVCV, the search for prophylactic or therapeutic solutions is thus relevant, particularly to identify solutions compatible with mass vaccination. In addition to being a threat to aquaculture and ecosystems, SVCV is a unique pathogen to study virus-host interactions in the zebrafish model. Establishing the first reverse genetics system for SVCV and the design of recombinant SVCV (rSVCV) expressing fluorescent or bioluminescent proteins adds a new dimension for the study of these interactions using innovative imaging techniques. The infection by bath immersion of zebrafish larvae with rSVCV expressing mCherry allows us to define the first SVCV replication sites and the host innate immune responses using different transgenic lines of zebrafish. The fins were found as the main initial sites of infection in both zebrafish and carp, its natural host. Hence, new insights into the physiopathology of SVCV infection have been described. We report that neutrophils are recruited at the sites of infection and persist up to the death of the animal leading to an uncontrolled inflammation correlated with the expression of the pro-inflammatory cytokine IL1β. Tissue damage was observed at the site of initial replication, a likely consequence of virus-induced injury or the pro-inflammatory response. Interestingly, SVCV infection by bath immersion triggers a persistent pro-inflammatory response rather than activation of the antiviral IFN signaling pathway as observed following intravenous injection, highlighting the importance of the route of infection on the progression of pathogenicity. Thus, this model of zebrafish larvae infection by rSVCV offers new perspectives to study in detail virus-host interactions and to discover new prophylactic or therapeutic solutions.
摘要：
鲤鱼病毒春季病毒血症（SVCV）具有广泛的鱼类宿主谱，是一种通常影响幼鱼的疾病的原因，死亡率高达90％。在没有针对SVCV的治疗或疫苗的情况下，因此，寻找预防性或治疗性解决方案是相关的，特别是确定与大规模疫苗接种相容的解决方案。除了对水产养殖和生态系统构成威胁之外，SVCV是在斑马鱼模型中研究病毒与宿主相互作用的独特病原体。建立第一个用于SVCV的反向遗传学系统以及表达荧光或生物发光蛋白的重组SVCV（rSVCV）的设计为使用创新的成像技术研究这些相互作用增加了新的维度。用表达mCherry的rSVCV对斑马鱼幼虫进行浸浴感染，使我们能够使用斑马鱼的不同转基因系定义第一个SVCV复制位点和宿主先天免疫反应。发现鳍是斑马鱼和鲤鱼的主要初始感染部位，它的自然宿主。因此，已经描述了对SVCV感染的病理生理学的新见解。我们报告说，嗜中性粒细胞在感染部位募集并持续到动物死亡，导致与促炎细胞因子IL1β表达相关的不受控制的炎症。在初始复制部位观察到组织损伤，病毒诱导的损伤或促炎反应的可能后果。有趣的是,SVCV感染通过浸浴引发持续的促炎反应，而不是如静脉注射后观察到的抗病毒IFN信号通路的激活，强调感染途径对致病性进展的重要性。因此，这种rSVCV感染斑马鱼幼虫的模型为详细研究病毒-宿主相互作用和发现新的预防或治疗方案提供了新的视角.
