Impact of virus-induced gill disease caused by carp edema virus (CEV) on the immunological status of fish

鳃病严重影响鱼类健康，对水产养殖造成很大的负面影响，这主要是因为鳃在鱼类生理上具有多种功能。由于缺乏专门影响鳃部的感染模型，对病原体相关的鳃部疾病的研究在很大程度上受到阻碍。鲤鱼水肿病毒（Carp edema virus， CEV）是一种感染鱼类的痘病毒，主要感染鲤鱼的鳃。它会诱发一种被称为锦鲤嗜睡病（KSD）的严重鳃病，对大多数受感染的鱼来说是致命的。由于其对鳃的严重影响，CEV感染对受感染的鱼造成生理上的痛苦，并似乎引起免疫功能的损害。有趣的是，不同品系的普通鲤鱼对这种病毒表现出高（黑龙江野生鲤鱼- AS品系）或低（锦鲤品系）的抗性。我们的工作假设提出：(i)不同的应激反应/应激敏感性可能影响锦鲤和鲤鱼AS株的KSD结果；（ii） KSD期间免疫反应的严重损害可能影响CEV感染后幸存者对继发感染的易感性和一般免疫状态。在本项目中，我们将研究AS和锦鲤品系之间对CEV抗性差异的机制。我们还将研究cev诱导的免疫反应损伤如何影响鲤鱼对其他病原体的易感性，如嗜branchophilum黄杆菌或CyHV-3病毒和鲤鱼病毒春季病毒血症（SVCV）。为了研究免疫功能下降的机制，我们将采用“盐拯救模型”，即在水族箱水中添加盐（NaCl），以消除CEV感染鱼的生理和免疫反应损伤。该项目的结果将使我们能够确定受病毒鳃病影响的鱼类的压力和免疫反应的相互作用及其对鱼类对临床疾病的抗性/易感性的重要性。最后，这些结果将使我们能够扩展我们对调节抗病毒免疫反应的重要和系统发育保守机制的知识。未来，对这种相互作用的深入了解将有助于制定预防和对抗病原体诱导的鳃疾病的新策略。

Gill diseases seriously affect fish health and have a high negative impact on aquaculture, mainly because of the multifunctional properties of gills in fish physiology. Studies on pathogen related gill diseases are largely hampered by the lack of infection models, which exclusively affect gills. Carp edema virus (CEV), a fish-infecting pox virus, infects predominantly the gills of common carp (Cyprinus carpio). It induces a severe gill disease known as koi sleepy disease (KSD) and is fatal for the majority of infected fish. Due to its severe effect on gills, the CEV infection causes physiological distress to infected fish and also seems to induce an impairment of the immunity. Interestingly, different strains of common carp show high (Amur wild carp - AS strain) or low (koi strain) resistance to this virus. Our working hypotheses propose that: (i) differential stress response/stress sensitivity might affect the outcome of KSD in koi and AS strains of carp and (ii) severe impairment of the immune response during KSD may have an impact on susceptibility to secondary infections and the general immunological status of the survivors after CEV infection. In the present project, we will study the mechanisms underlying the differences in the resistance to CEV between AS and koi carp strains. We will also study how a CEV-induced impairment of immune response influences the susceptibility of carp to other pathogens such as the bacterium Flavobacterium branchiophilum or the viruses cyprinid herpesvirus 3 (CyHV-3) and spring viraemia of carp virus (SVCV). To study the mechanisms of the immunity diminishing we will use a “salt rescue model” which is based on the supplementation of salt (NaCl) into the tank water, which abolishes the impairment of physiology and immune responses in CEV infected fish. The results of this project will allow us to identify the interplay of stress and immune responses in fish affected by a viral gill disease and its importance for resistance/susceptibility of fish to clinical disease. Finally, the results will allow us to expand our knowledge on important and phylogenetically conserved mechanisms regulating anti-viral immune response. In future, in-depth knowledge of such interactions will help to develop novel strategies for preventing and combating pathogen-induced gill diseases.