The 1918 HA and NA: Antigens and Virulence Factors

项目3,1918年HA和NA：抗原和毒力因子，试图使用反向遗传学、分子生物学、生化和血清学分析相结合的方法，进一步了解1918年病毒HA和NA蛋白在毒力中的分子水平贡献，并评估1918年病毒表面糖蛋白的抗原性新颖性。初步数据表明，1918年的HA和NA赋予小鼠Tumpey等人流感病毒高毒力表型。(2002年)PNAS 99,13849-54。这个项目将评估1918年大流行高死亡率的假设，即免疫幼稚人群的存在和1918年的其他特性都影响了这一假设 病毒HA和NA。含有1918个HA和NA基因的重组病毒的致病机制研究将在小鼠和鸡身上进行，并将进一步评估这些蛋白在毒力中的作用。此外，巴斯勒博士的实验室将根据陶本伯格博士生成的序列重建1918年基因的基因。这些重建的基因将被该计划项目的不同项目使用。

Project 3, The 1918 HA and NA: Antigens and Virulence Factors, seeks to use a combination of reverse genetics, molecular biological, biochemical and serological assays to further our understanding of the contributions at the molecular level, of the HA and NA proteins of the 1918 virus in virulence, and to assess the antigenic novelty of the 1918 surface glycoproteins. Preliminary data suggest that the 1918 HA and NA confer a high virulence phenotype upon influenza viruses in mice Tumpey, et al. (2002) PNAS 99, 13849-54. This project will evaluate the hypothesis that the high mortality rate of the 1918 pandemic was influenced both by the existence of an immunologically naive human population and by additional properties of the 1918 virus HA and NA. Pathogenesis studies of recombinant viruses containing 1918 HA and NA genes will be conducted in mice and chickens and will further evaluate the role of these proteins in virulence. In addition, Dr. Basler's laboratory will be reconstructing genes of the 1918 genes according to the sequences generated by Dr. Taubenberger. These reconstructed genes will be used by the different projects of the program project.