Microbiology and Parasitology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Université Paris-Saclay, INRAE, UVSQ, Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
PLoS Pathog. 2024 Aug 5;20(8):e1012328. doi: 10.1371/journal.ppat.1012328. eCollection 2024 Aug.
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.
锦鲤疱疹病毒（SVCV）具有广泛的宿主鱼类谱，是一种导致疾病的病原体，通常影响幼鱼，死亡率高达 90%。在没有针对 SVCV 的治疗方法或疫苗的情况下，因此寻找预防性或治疗性解决方案是相关的，特别是要找到与大规模疫苗接种兼容的解决方案。SVCV 不仅对水产养殖和生态系统构成威胁，而且是研究斑马鱼模型中病毒-宿主相互作用的独特病原体。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），为使用创新的成像技术研究这些相互作用增添了新的维度。通过浸泡感染斑马鱼幼虫 rSVCV 表达 mCherry，我们可以使用不同的斑马鱼转基因系来定义 SVCV 的第一个复制位点和宿主先天免疫反应。发现鱼鳍是斑马鱼和其天然宿主鲤鱼感染的主要初始部位。因此，对 SVCV 感染的病理生理学有了新的认识。我们报告说，中性粒细胞被招募到感染部位，并持续到动物死亡，导致与促炎细胞因子 IL1β的表达相关的失控性炎症。在初始复制部位观察到组织损伤，这可能是病毒诱导的损伤或促炎反应的结果。有趣的是，与静脉内注射观察到的情况相反，通过浸泡感染 rSVCV 会引发持续的促炎反应，而不是激活抗病毒 IFN 信号通路，这突出了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性或治疗性解决方案提供了新的视角。
