A型流感病毒的核质穿梭及其对病毒复制的影响

Influenza A viruses transcribe and replicate their genomes in the nuclei of infected host cells. Nuclear-cytoplasmic shuttling of viral proteins occurs throughout the entire virus life cycle. Although some nuclear-cytoplasmic shuttling-associated NLSs/NESs, phosphorylation sites, and SUMOylation sites have been found successively in influenza A virus, their functions are still not clear. In our previous studies, we have identified several of NLSs/NESs and phosphorylation sites of NP/NEP/M1 protein of influenza A virus and explored some of their functions. In this proposal, we will identify a series of potential nuclear-cytoplasmic shuttling-associated NLSs/NESs, phosphorylation sites, SUMOylation sites, and host proteins, and then investigate the mechanisms of nuclear-cytoplasmic shuttling and the regulation of virus replication through the phosphorylation or SUMOylation to further understand the regulation of nuclear-cytoplasmic shuttling in host adaptation of influenza A virus. It will provide insights for understanding the interspecies transmission of influenza virus and finding potential targets for antiviral drugs.

A型流感病毒是一种在细胞核内进行基因组转录和复制的RNA病毒，其病毒蛋白的核质穿梭在病毒复制过程中起着至关重要的作用。目前已有一些A型流感病毒核质穿梭相关的NLS/NES信号肽、宿主蛋白、磷酸化和类泛素化位点被陆续发现，但大部分功能尚不明确。我们的前期研究筛选了部分流感蛋白的NLS/NES和磷酸化位点，并对其在核质穿梭和病毒复制中的作用进行了初步研究。本项目拟在此基础上利用分子与细胞生物学、生物信息学等手段，进一步筛选与确定一系列影响A型流感病毒核质穿梭的NLS/NES、宿主因子、磷酸化位点和类泛素化位点；全面系统地分析病毒的核质穿梭过程及其对病毒复制的影响；阐明A型流感病毒蛋白的磷酸化/类泛素化对核质穿梭及病毒复制的调控机制；明确病毒蛋白的核质穿梭与宿主适应性的关系。该研究有助于加深对流感病毒核质穿梭过程的认识，并为以核质穿梭为靶点的抗病毒药物的设计以及病毒的跨种间传播研究提供理论依据。