新亚型汉坦病毒包膜蛋白在汉坦病毒感染与致病中的作用

肾综合征出血热（HFRS）由汉坦病毒引起，近年来流行趋势已经改变，病毒基因变异是HFRS流行趋势改变的主要原因，研究发现流行于世界不同地区的病毒有30多个基因型，但对其致病性所知甚少。因此，阐明这些不同基因型病毒功能是解释HFRS流行趋势改变的关键所在。由于病毒M基因编码的G蛋白决定了病毒的感染性及毒力，且变异显著。本项目拟在前期获得大量新型汉坦病毒毒株及基因信息的基础上，进一步分析这些病毒G蛋白的抗原性差异及在HFRS流行中的作用，再用恒河猴证明这些新病毒的感染性与致病性差异。然后，构建含有汉坦病毒G蛋白的假病毒系统，研究这些新病毒G蛋与细胞表面受体的相互作用位点和中和表位，证明与致病相关的关键基因位点与蛋白的功能，阐明这些新型病毒致病的分子机制，评价其在HFRS发生与流行中的作用。它对于控制HFRS的流行有重要的理论指导意义。

The epidemic trend of hemorrhagic fever with renal syndrome (HFRS) caused by hantavirus have changed in recent years.The epidemiological characteristics of HFRS are regional, explosive and changeable. Based on the etiology, the mutation of viral gene was the main cause of the changing trend. More than 30 genotypes of hantavirus have been identified and classified in different areas of the world, but little is know about their pathogenicity. Hence, illustrating the protein's function of different novel hantaviruses is the key to elucidate the changing trend of HFRS.The cell tropism, infectivity and virulence of hantavirus are detemined by the G protein which is encoded by M gene. Based on our previous research on genetic evolutionary analysis, this project aims to further analyze the antigenicity difference and the impact on epidemic of G protein of novel subtype hantaviruses. In addition, Rhesus monkey will be applied for evaluation the infectivity and pathogenic of the subtypes. By means of constructing pseudotypvirus bearing the glycoproteins of the novel subtype hantavirus, the key domain involved in interacting with the receptors and neutralizing epitope will be also determined. To clarify the disease-causing molecular mechanism of the novel subtypes and evaluate their role in the occurrence and epidemic of HFRS could help us to predict the developments and future threats of these emerging pathogens.