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，对水产养殖业产生很大的负面影响，主要是因为鳃在鱼类生理中的多功能特性。病原体相关的鳃疾病的研究在很大程度上阻碍了缺乏感染模型，这只影响鳃。鲤鱼水肿病毒（CEV）是一种感染鱼类的痘病毒，主要感染鲤鱼（Cyprinus carpio）的鳃。它会引起一种严重的鳃病，称为锦鲤嗜睡病（KSD），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感染引起受感染的鱼的生理痛苦，并且似乎还诱导免疫力的损害。有趣的是，不同的鲤鱼品系对该病毒表现出高（阿穆尔野生鲤鱼- AS品系）或低（锦鲤品系）抗性。我们的工作假设提出：（i）不同的应激反应/应激敏感性可能会影响锦鲤和鲤鱼AS株KSD的结果和（ii）KSD期间免疫反应的严重受损可能会影响继发感染的易感性和CEV感染后幸存者的一般免疫状态。在本项目中，我们将研究AS和锦鲤品系对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，如细菌Flavobacterium branchiophilum或病毒鲤疱疹病毒3（CyHV-3）和鲤鱼病毒春季病毒血症（SVCV）。为了研究免疫力下降的机制，我们将使用“盐拯救模型”，该模型基于向水箱水中补充盐（NaCl），其消除了CEV感染鱼的生理和免疫应答的损害。 该项目的结果将使我们能够确定受病毒性鳃病影响的鱼类的应激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大我们对重要的和遗传上保守的机制调节抗病毒免疫反应的知识。在未来，深入了解这种相互作用将有助于开发新的战略，预防和打击病原体引起的鳃疾病。

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.