许多研究表明，核定位信号（NLS）介导的病毒蛋白细胞核定位对病毒复制增殖具有重要作用。新城疫病毒（NDV）M蛋白是病毒感染期间唯一能通过自身携带的NLS进入细胞核的病毒蛋白，对NLS中关键氨基酸位点突变可以破坏M蛋白的细胞核定位特征。我们前期利用反向遗传操作技术拯救出M蛋白NLS突变的NDV，初步研究发现与野生型病毒相比，突变体病毒的复制增殖能力显著下降，但是这种作用机制尚不清楚。本项目拟通过研究M蛋白NLS突变对NDV生物学特性、基因组复制转录水平以及病毒装配和出芽效率的影响，筛选和分析M蛋白NLS突变型和野生型NDV感染细胞后的差异表达蛋白，并对其在NDV复制增殖中的作用进行功能验证，以此阐明M蛋白NLS突变影响NDV复制增殖的作用机制。本研究工作的开展对我们深入了解NLS介导的NDV M蛋白细胞核定位功能、研究M蛋白在NDV复制和致病机制中的作用具有重要意义。

Numerous studies have shown that the nuclear localization of viral proteins mediated by nuclear localization signal (NLS) plays crucial roles in the replication and proliferation of viruses. The M protein of Newcastle disease virus (NDV) is demonstrated to localize in the nucleus via its own NLS, which is essential for the nuclear localization characteristics of M protein. We previously rescued the NDV carrying M/NLS mutation using reverse genetics and found that the replication and proliferation ability of the mutant NDV dropped significantly when compared to the wild-type NDV. However, the mechanism of the effect of M/NLS mutation on the replication and proliferation of NDV remains unknown. This project planned to study the effect of M/NLS mutation on the biological characteristics, the level of genome replication and transcription, and the efficiency of assembly and budding of NDV; screen and analyze the differentially expressed proteins derived from M/NLS mutant and wild-type NDV infected cells. Moreover, the function of these proteins in the replication and proliferation of NDV was verified. The results obtained from the project could reveal the mechanism of the obvious reduction of NDV replication and proliferation affected by M/NLS mutation. The research work will be of great importance in understanding the function of M’s nuclear localization, and studying the role of M protein in the replication and pathogenic mechanism of NDV.