PDF(Pubmed)
Abstract：
Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body\'s immune response; however, its specific role in the IFN-guided immune response in fish is yet to be clarified. In this study, we characterized foxo3 in Japanese medaka (Oryzias latipes) and examined its role in the IFN-dependent immune response upon infection with the RGNNV. The results show that the coding region of the medaka foxo3 gene is 2007 base pairs long, encoding 668 amino acids, and possesses a typical forkhead protein family structural domain. The product of this gene shares high homology with foxo3 in other fish species and is widely expressed, especially in the brain, eyes, testes, and heart. Upon RGNNV infection, foxo3-/- mutant larvae showed a lower mortality rate, and adults exhibited a significant reduction in virus replication. Moreover, the absence of foxo3 expression led to an increase in the expression of irf3, and a decrease in the expression of other IFN-related genes such as tbk1 and mapk9, implying that foxo3 may function as a negative regulator in the antiviral signaling pathway. These findings provide crucial insights for disease-resistant breeding in the aquaculture industry.
摘要：
遇到病毒时，鱼类启动先天免疫反应，由IFNs指导。Foxo3在人体的免疫反应中起着一定的作用；然而，其在鱼类IFN指导的免疫应答中的具体作用尚待阐明。在这项研究中,我们在日本medaka（Oryziaslatipes）中表征了foxo3，并检查了其在感染RGNNV后的IFN依赖性免疫反应中的作用。结果表明，medakafoxo3基因的编码区长为2007个碱基对，编码668个氨基酸，并具有典型的叉头蛋白家族结构域。该基因的产物与其他鱼类中的foxo3具有很高的同源性，并广泛表达，尤其是在大脑中，眼睛,睾丸,和心脏。在RGNNV感染后,foxo3-/-突变幼虫的死亡率较低，成人表现出病毒复制的显著减少。此外，foxo3表达的缺失导致irf3的表达增加，其他IFN相关基因如tbk1和mapk9的表达减少，这意味着foxo3可能在抗病毒信号通路中起负调节因子的作用。这些发现为水产养殖业的抗病育种提供了重要见解。
