Holmlund Ingrid, Ahmadi Samira, Ruyter Bente, Østbye Tone-Kari, Bou Marta, Gjøen Tor
University of Oslo, Oslo, Norway.
Nofima, Ås, Norway.
Virol J. 2025 Jan 9;22(1):5. doi: 10.1186/s12985-024-02619-0.
Aquaculture is one of the world's fastest-growing sectors in food production but with multiple challenges related to animal handling and infections. The disease caused by infectious salmon anemia virus (ISAV) leads to outbreaks of local epidemics, reducing animal welfare, and causing significant economic losses. The composition of feed has shifted from marine ingredients such as fish oil and fish meal towards a more plant-based diet causing reduced levels of eicosapentaenoic acid (EPA). The aim of this study was to investigate whether low or high levels of EPA affect the expression of genes related to the innate immune response 48 h after infection with ISAV. The study includes seven experimental groups: ± ISAV and various levels of EPA up to 200 µM. Analysis of RNA sequencing data showed that more than 3000 genes were affected by ISAV alone (without additional EPA). In cells with increasing levels of EPA, more than 2500 additional genes were differentially expressed. This indicates that high levels of EPA concentration have an independent effect on gene expression in virus-infected cells, not observed at lower levels of EPA. Analyses of enriched biological processes and molecular functions (GO and KEGG analysis) revealed that EPA had a limited impact on the innate immune system alone, but that many processes were affected by EPA when cells were virus infected. Several biological pathways were affected, including protein synthesis (ribosomal transcripts), peroxisome proliferator activated receptor (PPAR) signaling, and ferroptosis. Cells exposed to both increasing concentrations of EPA and virus displayed gene expression patterns indicating increased formation of oxygen radicals and that cell death via ferroptosis was activated. This gene expression pattern was not observed during infection at low EPA levels or when Atlantic salmon kidney (ASK) cells were exposed to the highest EPA level (200 μM) without virus infection. Cell death via ferroptosis may therefore be a mechanism for controlled cell death and thus reduction of virus replication when there are enough polyunsaturated fatty acids (PUFAs) in the membrane.
水产养殖是世界上食品生产中增长最快的部门之一，但在动物处理和感染方面面临多重挑战。由传染性鲑鱼贫血病毒（ISAV）引起的疾病会导致局部疫情爆发，降低动物福利，并造成重大经济损失。饲料的成分已从鱼油和鱼粉等海洋成分转向更多基于植物的饮食，导致二十碳五烯酸（EPA）水平降低。本研究的目的是调查低水平或高水平的EPA是否会影响感染ISAV 48小时后与先天免疫反应相关基因的表达。该研究包括七个实验组：±ISAV以及高达200μM的不同水平的EPA。RNA测序数据分析表明，仅ISAV（无额外EPA）就影响了3000多个基因。在EPA水平升高的细胞中，另外有2500多个基因差异表达。这表明高水平的EPA浓度对病毒感染细胞中的基因表达有独立影响，而在低水平的EPA中未观察到这种影响。对富集的生物学过程和分子功能（GO和KEGG分析）的分析表明，EPA单独对先天免疫系统的影响有限，但当细胞被病毒感染时，许多过程会受到EPA的影响。包括蛋白质合成（核糖体转录本）、过氧化物酶体增殖物激活受体（PPAR）信号传导和铁死亡在内的几种生物学途径受到影响。暴露于EPA浓度增加和病毒的细胞显示出基因表达模式，表明氧自由基形成增加，并且通过铁死亡的细胞死亡被激活。在低EPA水平感染期间或大西洋鲑鱼肾（ASK）细胞在无病毒感染的情况下暴露于最高EPA水平（200μM）时，未观察到这种基因表达模式。因此，当膜中有足够的多不饱和脂肪酸（PUFA）时，通过铁死亡的细胞死亡可能是一种控制细胞死亡从而减少病毒复制的机制。
