季节性H3N2流感PB1-F2断裂株监测与致病性研究

PB1-F2是甲流病毒的非结构蛋白，具有诱导宿主细胞凋亡、增加肺部细菌感染、上调病毒RNA聚合酶活性等功能，是重要毒力因子。甲型流感的PB1-F2基因呈现一定进化特征；不同亚型甲流毒株编码的PB1-F2蛋白功能存在差异。H3N2是监测的流行株之一，课题组于2010年首次监测到（2011年再次监测到）我国季节性H3N2病毒PB1-F2蛋白断裂株，提示我国目前H3N2流感PB1-F2完整和断裂株同时存在。本课题结合基因序列分析和反向遗传学技术，通过动物实验、哨点监测和个案调查，监测季节性H3N2流感PB1-F2完整/断裂株在流感样人群和住院流感患者中的感染情况；研究季节性H3N2流感PB1-F2基因进化特征；研究完整/断裂PB1-F2蛋白功能；综合分析现场监测、个案调查和动物试验的结果，探讨H3N2流感PB1-F2蛋白完整/断裂株感染与临床表现的关系，为季节性H3N2流感防制提供依据。

The recently discovered PB1-F2 is one kind of non-structural protein of influenza A viruses (IAVs), PB1-F2 is recognized as an important virulence factor because it can induce apoptosis in host cells, promote bacterial infections in lung, increase the viral RNA polymerase activity and posses other functions. As present studies shown, PB1-F2 gene of IAVs had developed in specific evolutionary characteristics, and functions of PB1-F2 encoded by different IAVs subtypes were strain specific. H3N2 subtype viruses are important in seasonal epidemic of influenza, our group had discovered seasonal H3N2 IAVs that can encode truncated PB1-F2 protein in 2010, which was the first time surveyed in Chinese mainland, and this kind of PB1-F2 gene was detected again in 2011; It was a indication that H3N2 influenza viruses encoded complete and truncated PB1-F2 both existed in current epidemics, further surveillance on PB1-F2 gene should be carried to study its prevalence in the future. In addition, the functions of this phenotype of PB1-F2 gene are still unknown, so this subject will launch animal experiments, sentinel surveillance and case investigation, to monitor the prevalence of complete/truncated PB1-F2 in seasonal H3N2 influenza strains that are isolated in the influenza-like illnesses and hospitalized influenza patients; Evolutionary characteristics and functions of complete/truncated PB1-F2 protein in seasonal H3N2 influenza will be studied by combining gene sequence analysis and reverse genetic techniques, respectively. Comprehensive analysis of field monitoring, case investigation and animal experiments will be carried to explore the relationships between infection of different H3N2 influenza viruses and clinical manifestations in influenza patients, and to provide basis for the prevention and control of seasonal influenza.