狂犬病毒（RV）和乙型脑炎病毒（JEV）是当前严重危害人畜健康的病原。病毒与免疫系统相互博弈是病毒入侵的第一步，当宿主免疫力下降时，不仅增加病毒感染机体的可能，也降低了疫苗免疫原性导致免疫失败。研究发现，日常治疗慢性炎症的不饱和脂肪酸（ω-3），不仅抑制免疫细胞激活和炎症反应，而且降低宿主对细菌性病原的抵抗能力。申请人发现ω-3过表达抑制树突状细胞（DCs）的激活和DCs的抗病毒反应，我们推测ω-3在RV和JEV致病和免疫逃避中扮演重要角色。为证实以上假设，通过培养DCs，流式细胞术和蛋白印迹等技术，研究ω-3受体GPR120通过TAK1影响下游MKK4和IkappaB，并对DCs抗RV和JEV感染能力的影响。用小鼠模型分别检测ω-3对RV和JEV致死率的影响及ω-3对RV和JEV疫苗免疫效果的影响。本项目首次研究过量ω-3导致免疫抑制从而降低抗病毒免疫反应，为RV和JEV防治提供新思路。

Rabies virus (RV) and Japanese encephalitis virus (JEV) are major causative agents of zoonosis. The first step of these virus entering into host are fighting with host immune system. However, when the host immune system was downregulated, the virus infection would upregulate and the vaccine immune would be abortive. Recently, some researchers have reported that dietary omega-3 fatty acids (ω-3) depress immune cell activation and impair the immune response against bacterial pathogens infection, but the ω-3 could affect virus infection which has not been study. In the recent study, the applicant found that the dendritic cells (DCs) of ω-3 over expressing will have low immune sensitization and poor virus control. Therefore, the hypothesis is ω-3 plays a key role in regulating the immune evasion of RV and JEV. To demonstrate that, we use DCs in vitro culture system, flow cytometry and western blot to study the receptor of ω-3 through TAK1 kinase depressing MKK4 and IkappaB to regulate DCs activation, which affect DCs infections immunity of RV and JEV. Further, in vivo research to study the survival rate of mouse challenge with wild type RV and JEV after ω-3 treatment, or the immune response of mouse vaccinated with lab attenuated RV and JEV after ω-3 treatment. This present study 1st time show ω-3 induce immune suppression to reduce host defending viral infection, which will provide a novel stratagem to compete with RV and JEV infection.