中文摘要：研究分别采用pIFNa、pHE、质粒对照（pcDNA3.3）和PBS注射三文鱼肌肉，比较了1-2周后肌肉注射部位的转录反应。结果表明，IFNa质粒介导了注射肌肉至少3种类型的基因转录的增加，分别为典型的IFN-I诱导基因（ISGs）、B细胞主要化学增活素和标记、T细胞和抗原呈递细胞；后者表明了这些细胞在质粒注射部位的富集。淋巴细胞的富集可能是由与哺乳动物CCL5、CCL8、CCL19和CXCL10同源的化学增活素引起的。IFN同时可能参与淋巴细胞激活，这与哺乳动物的研究结果是抑制的。本研究的主要发现是，pcDNA3.3和pHE能够诱导产生相似的抗pIFNa的免疫反应，但量较低。质粒DNA具有佐剂活性。值得一提的是，pHE对包括ISGs、化学增活素等免疫基因的作用低于pcDNA3.3，这表明HE表达对免疫基因具有抑制作用。研究结果表明，pIFNa对抗ISAV DNA疫苗的佐剂作用可以克服HE表达对质粒介导的ISGs和化学增活素的抑制作用。
外文摘要：A previous study showed that a plasmid expressing IFNa (pIFNa) strongly enhanced protection and antibody production of a DNA vaccine against infectious salmon anemia virus (ISAV) in Atlantic salmon. The vaccine consisted of a plasmid (pHE) expressing the virus hemagglutinin-esterase as an antigen. To increase the understanding of the adjuvant effect of pIFNa, we here compared transcriptome responses in salmon muscle at the injection site at week 1 and 2 after injection of pIFNa, pHE, plasmid control (pcDNA3.3) and PBS, respectively. The results showed that the IFNa plasmid mediates an increase in gene transcripts of at least three major types in the muscle; typical IFN-I induced genes (ISGs), certain chemokines and markers of B-cells, T-cells and antigen-presenting cells. The latter suggests recruitment of cells to the plasmid injection site. Attraction of lymphocytes was likely caused by the induction of chemokines homologous to mammalian CCL5, CCL8, CCL19 and CXCL10. IFN may possibly also co-stimulate activation of lymphocytes as suggested by studies in mammals. A major finding was that both pcDNA3.3 and pHE caused responses similar to pIFNa, but at lower magnitude. Plasmid DNA may thus by itself have adjuvant activity as observed in mammalian models. Notably, pHE had a lower effect on many immune genes including ISGs and chemokines than pcDNA3.3, which suggests an inhibitory effect of HE expression on the immune genes. This hypothesis was supported by an Mx-reporter assay. The present study thus suggests that a main role for pIFNa as adjuvant in the DNA vaccine against ISAV may be to overcome the inhibitory effect of HE-expression on plasmid-induced ISGs and chemokines.
外文关键词：HEMATOPOIETIC NECROSIS VIRUS; ATLANTIC SALMON; RAINBOW-TROUT; CHEMOKINE RECEPTORS; B-CELLS; IMMUNE-RESPONSES; MX1 PROMOTER; T-CELLS; INTERFERON; EXPRESSION
作者：Sobhkhez, M; Krasnov, A; Chang, CJ; Robertsen, B
作者单位：挪威北极大学
期刊名称：PLOS ONE
期刊影响因子：0.0
出版年份：3.11
出版刊次：2017
点击下载：对质粒诱导基因的转录组分析能够揭示IFN对三文鱼贫血症病毒DNA疫苗的佐剂作用