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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.

草鱼春病毒血症（SVCV）具有广泛的鱼类宿主谱，通常导致影响幼鱼的疾病，其死亡率高达90%。鉴于目前尚无针对SVCV的治疗或疫苗，因此寻找预防或治疗性解决方案显得尤为重要，尤其是那些与大规模疫苗接种相兼容的方案。SVCV不仅对水产养殖和生态系统构成威胁，而且作为斑马鱼模型中研究病毒-宿主相互作用的一种独特病原体，具有研究价值。建立了SVCV的第一个反向遗传学系统，并设计了表达荧光或生物发光蛋白的重组SVCV（rSVCV），这为利用创新成像技术研究这些相互作用提供了新的维度。通过浸泡斑马鱼幼虫的浴液感染rSVCV表达mCherry蛋白，使我们能够确定SVCV的第一个复制位点以及宿主的天然免疫反应，这得益于斑马鱼的不同转基因系。研究发现，鳍是斑马鱼和其自然宿主草鱼感染的主要初始部位。因此，关于SVCV感染病理生理学的新见解得以阐述。我们报道，中性粒细胞在感染部位被招募并持续至动物死亡，导致与促炎细胞因子IL1β表达相关的失控性炎症。在初始复制部位观察到组织损伤，这可能是病毒引起的损伤或促炎反应的后果。有趣的是，通过浸泡感染SVCV触发的持续促炎反应，而非如静脉注射后所观察到的抗病毒IFN信号通路激活，突出了感染途径在病原性进展中的重要性。因此，通过rSVCV感染斑马鱼幼虫的模型为详细研究病毒-宿主相互作用以及发现新的预防或治疗性解决方案提供了新的视角。