核糖核苷酸还原酶M2影响J亚群禽白血病病毒增殖的作用机制

J亚群禽白血病是由ALV-J引起的严重危害养禽业的肿瘤性疾病。虽然在ALV感染与防控方面受到广泛关注, 但目前ALV-J的致病机理尚不十分清楚。本团队在前期研究中发现，ALV通过衣壳蛋白P27影响Wnt/β-catenin信号转导，并筛选到与P27互作的宿主蛋白RRM2。由于RRM2在调控DNA合成和细胞增殖过程中具有重要作用，因此探明RRM2影响J亚群禽白血病病毒增殖的作用机制具有重要意义。本项目重点研究RRM2与P27互作调控Wnt/β-catenin信号转导机制以及RRM2关键氨基酸位点生化修饰对ALV-J增殖的影响，探索RRM2在ALV-J感染过程中的作用与机理，为深入解析ALV-J的致病机制提供科学依据，并为J亚群禽白血病的防控提供新的思路。

Subgroup J avian leukosis caused by subgroup J avian leukosis virus (ALV-J) is an infectious neoplastic disease which has been seriously plaguing poultry industry. In our previous study, an essential gene (RRM2) screened in the purebred chicken with high ALV-J resistance is mainly involved in DNA synthesis and cell proliferation. However, the underlying molecular mechanism of RRM2 on ALV-J replication is still unclear. Based on our findings that ALV-J infection is associated with the activation of Wnt/β-catenin signaling pathway, capsid protein P27 plays a critical role during the process, and RRM2 interacts with P27. We further investigate the molecular mechanism of RRM2 regulating ALV-J replication using co-immunoprecipitation, confocal microscopy and dual-luciferase reporter gene system. This study will clarify the effect of P27-RRM2 interaction on Wnt/β-catenin signaling pathways and understand the effect of RRM2 protein modification on ALV-J proliferation. This project will definitely have an important theoretical and practical meaning in subgroup J avian leukosis prevention.