MOLECULAR GENETICS OF INFLUENZA VIRUS HEMAGGLUTININ

流感病毒仍然是人类不受控制的病原体之一。 该建议旨在了解生物合成，结构 和功能的血凝素（HA）糖蛋白，主要 流感病毒包膜的组成部分。 在研究中， 直接针对病毒的生命周期， 遗传学将用于分析HA在肿瘤中的生物学作用。 感染性和病毒体进入宿主细胞和 宿主机体对感染的免疫反应 的研究 HA的生物合成将阐明 是蛋白质加工、成熟和细胞内转运的基础， 真核生物糖蛋白。 这些具体目标 研究包括： 1.为了鉴定HA中有助于 低pH诱导的膜融合活性 分子。 2.为了分析保守氨基酸在蛋白质合成中的作用， 在流感病毒体的出芽中HA的胞质尾区。 3.分析蛋白质结构在蛋白质水解中的作用， 激活HA，并研究细胞的位置， 进行这种切割的蛋白酶。 4.研究流感病毒的细胞免疫应答 通过分析不同的呈现方式来分析病毒感染 HA抗原对细胞毒性淋巴细胞的作用。 5.为了继续研究蛋白质折叠在 HA的细胞内转运。 6.为了识别和表征 HA突变体被阻止的胞吐途径。

Influenza virus remains one of the uncontrolled pathogens of man. This proposal is aimed at understanding the biosynthesis, structure and function of the hemagglutinin (HA) glycoprotein, the major component of the influenza virus envelope. In studies pertaining directly to the life cycle of the virus, techniques of molecular genetics will be used to analyze the biological roles of HA in the infectivity and entry of the virion into the host cell and in the host organism's immune response to infection. Studies of the biosynthesis of HA will elucidate the cellular mechanisms that underly the processing, maturation and intracellular transport of eukaryotic glycoproteins in general. The specific aims of these studies are: 1. To identify individual amino acids in HA that contribute to the low pH-induced membrane fusion activity of the molecule. 2. To analyze the role of conserved amino acids in the cytoplasmic tail of HA in the budding of influenza virions. 3. To analyze the role of protein structure in the proteolytic activation of HA and to investigate the location of cellular proteases that carry out this cleavage. 4. To investigate the cellular immune response to influenza virus infection by analyzing different modes of presentation of the HA antigen to cytotoxic lymphocytes. 5. To continue to study the role of protein folding in the intracellular transport of HA. 6. To identify and characterize compartments of the exocytotic pathway in which HA mutants become arrested.