Table_10_Integrative Transcriptomic Analysis Reveals the Immune Mechanism for a CyHV-3-Resistant Common Carp Strain.xlsx

Anti-disease breeding is becoming the most promising solution to cyprinid herpesvirus-3 (CyHV-3) infection, the major threat to common carp aquaculture. Virus challenging studies suggested that a breeding strain of common carp developed resistance to CyHV-3 infection. This study illustrates the immune mechanisms involved in both sensitivity and anti-virus ability for CyHV3 infection in fish. An integrative analysis of the protein-coding genes and long non-coding RNAs (lncRNAs) using transcriptomic data was performed. Tissues from the head kidney of common carp were extracted at days 0 (the healthy control) and 7 after CyHV-3 infection (the survivors) and used to analyze the transcriptome through both Illumina and PacBio sequencing. Following analysis of the GO terms and KEGG pathways involved, the immune-related terms and pathways were merged. To dig out details on the immune aspect, the DEGs were filtered using the current common carp immune gene library. Immune gene categories and their corresponding genes in different comparison groups were revealed. Also, the immunological Gene Ontology terms for lncRNA modulation were retained. The weighted gene co-expression network analysis was used to reveal the regulation of immune genes by lncRNA. The results demonstrated that the breeding carp strain develops a marked resistance to CyHV-3 infection through a specific innate immune mechanism. The featured biological processes were autophagy, phagocytosis, cytotoxicity, and virus blockage by lectins and MUC3. Moreover, the immune-suppressive signals, such as suppression of IL21R on STAT3, PI3K mediated inhibition of inflammation by dopamine upon infection, as well as the inhibition of NLRC3 on STING during a steady state. Possible susceptible factors for CyHV-3, such as ITGB1, TLR18, and CCL4, were also revealed from the non-breeding strain. The results of this study also suggested that Nramp and PAI regulated by LncRNA could facilitate virus infection and proliferation for infected cells respectively, while T cell leukemia homeobox 3 (TLX3), as well as galectin 3 function by lncRNA, may play a role in the resistance mechanism. Therefore, immune factors that are immunogenetically insensitive or susceptible to CyHV-3 infection have been revealed.

抗病育种已成为防治草鱼三代病毒（CyHV-3）感染的最有前景的解决方案，该病毒是草鱼养殖的主要威胁。病毒挑战研究指出，草鱼育种株对CyHV-3感染表现出抵抗力。本研究阐述了鱼类对CyHV3感染敏感性和抗病毒能力所涉及的免疫机制。通过对转录组数据进行蛋白质编码基因和长非编码RNA（lncRNA）的整合分析，提取了草鱼头肾组织，分别在CyHV-3感染后0天（健康对照组）和7天（存活组）进行提取，并利用Illumina和PacBio测序技术分析转录组。在分析涉及的GO术语和KEGG通路后，将免疫相关术语和通路进行整合。为深入挖掘免疫方面的细节，利用当前草鱼免疫基因库对差异表达基因（DEGs）进行筛选。揭示了不同比较组中的免疫基因类别及其对应基因。同时，保留了lncRNA调节的免疫学Gene Ontology术语。通过加权基因共表达网络分析揭示了lncRNA对免疫基因的调控作用。结果显示，育种草鱼株通过特定的天然免疫机制对CyHV-3感染产生了显著的抵抗力。特征性生物学过程包括自噬、吞噬、细胞毒性和通过凝集素和MUC3阻断病毒。此外，还揭示了免疫抑制信号，如感染时IL21R对STAT3的抑制、多巴胺介导的PI3K对炎症的抑制，以及在稳态下NLRC3对STING的抑制。从非育种株中揭示了CyHV-3的可能易感因素，如ITGB1、TLR18和CCL4。本研究的结果还表明，受LncRNA调控的Nramp和PAI分别可促进病毒感染和感染细胞的增殖，而T细胞白血病同源盒3（TLX3）以及通过LncRNA发挥功能的半乳糖凝集素3可能参与抵抗机制。因此，揭示了那些对CyHV-3感染免疫遗传上不敏感或易感的免疫因素。