神经坏死病毒可严重危害鱼苗，至今对其防控还缺高效措施。病毒复制研究可为其防控提供新依据。我们前期研究表明，谷氨酰胺是神经坏死病毒复制所必须，其通过三羧酸循环途径影响病毒复制，但机理未知。C-Myc可调控多种动物谷氨酰胺代谢，但鱼类相应研究还鲜有报道。我们发现神经坏死病毒感染可上调C-Myc表达；病毒衣壳蛋白可进入细胞核、结合并上调表达C-Myc蛋白。据此，我们提出假设：神经坏死病毒衣壳蛋白激活C-Myc蛋白来调控宿主谷氨酰胺分解代谢。主要研究内容有：[1]病毒衣壳蛋白和C-Myc蛋白结合的结构域；[2]核定位对衣壳蛋白和C-Myc互作的影响；[3]C-Myc调控细胞谷氨酰胺代谢和病毒复制的关系；[4]谷氨酰胺分解代谢和病毒复制能量（ATP）关系；[5]谷氨酰胺依赖的谷胱甘肽合成和病毒复制的关系。本研究结果将加深我们对神经坏死病毒复制的认识，同时也为该病毒的高效防控提供新的理论依据。

Nervous necrosis virus (NNV) is a pathogen which can infect a wide range of young fish with high mortality. However, there is lack of effective strategy against the NNV infection. The knowledge about the viral replication can pave a new way for the development of effective strategy against viral infection. We have reported previously that glutamine was required for red-spotted grouper nervous necrosis virus replication via replenishing the tricarboxylic acid cycle. However, how NNV regulates the catabolism of glutamine remains enigmatic. There have been many reports that over expression of C-Myc protein can enhance the catabolism of glutamine in human beings and many other animals. However, the regulation of glutamine via C-Myc in fish is still not characterized. In our previous studies, we observed that the capsid protein of NNV can enter the nucleus where it can bind to C-Myc as well as enhance the expression of C-Myc. Basing on the above observations, we propose the following hypothesis: “Nervous necrosis virus regulates cellular glutamine catabolism via activation of C-Myc by vial capsid protein”. In this proposal, we will perform the following studies：[1] Mapping the detailed domains which are required for the interactions of the viral capsid protein and C-Myc protein. [2] Figure out whether the location in the nucleus is essential for the interactions of the viral capsid protein and C-Myc protein. [3] The relationship between glutamine catabolism regulated by C-Myc in grouper cell line and NNV replication. [4] The relationship between the ATP generated from the catabolism of glutamine and NNV replication. [5] The relationship between the pathway of glutathione synthesis via glutamine catabolism and NNV replication. The obtained results from this proposal will shed a new light on the NNV replication and will pave a new way for the prevention of NNV infection.