The 1918 HA and NA: Antigens and Virulence Factors

1918 HA 和 NA：抗原和毒力因子

• 批准号: 7662462
• 负责人: Christopher F Basler
• 金额: $ 21.33万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7662462
• 关键词: Animal Model; Antigens; Avian Influenza A Virus; Biochemical; Biological; Biological Assay; Birds; Characteristics; Chickens; Cultured Cells; Data; Endopeptidases; Genes; Genetic Determinism; Growth; Hemagglutinin; Human; Influenza; Influenza A Virus, H1N1 Subtype; Laboratories; Life; Maps; Membrane Glycoproteins; Methods; Molecular; Mus; Neuraminidase; Pathogenesis; Peptide Hydrolases; Phenotype; Population; Primates; Property; Proteins; Rate; Role; Serological; Serum; Site; Specimen; Structure; Surface Antigens; Tissues; Trypsin; Viral; Virulence; Virulence Factors; Virulent; Virus; Virus Diseases; base; influenza virus gene; influenzavirus; mortality; neutralizing antibody; pandemic disease; pandemic influenza; positional cloning; programs; recombinant virus; reconstruction; success; tissue culture; virology

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.

项目3，1918年的HA和NA：抗原和毒力因素，试图将反向遗传学，分子生物学，生化和血清学测定法的结合进一步，以进一步了解我们对1918病毒毒力的HA和Na蛋白在毒力中的HA和Na蛋白上的贡献的理解，以评估1918年的抗原性新颖性GGLEDCORT。初步数据表明，1918年的HA和NA赋予小鼠Tumpey小鼠病毒的高毒力表型。 （2002）PNAS 99，13849-54。该项目将评估以下假设，即1918年大流行的高死亡率受到免疫幼稚的人口的影响以及1918年的其他特性 病毒HA和NA。将在小鼠和鸡中对含有1918年HA和Na基因的重组病毒进行发病机理研究，并将进一步评估这些蛋白质在毒力中的作用。此外，Basler博士的实验室将根据Taubenberger博士产生的序列重建1918年基因的基因。这些重建基因将由程序项目的不同项目使用。