FOLDING ASSEMBLY, AND TRANSPORT OF VIRAL GLYCOPROTEINS

现有抗病毒疫苗的改进和 新型疫苗取决于我们对病毒的了解 附着和融合糖蛋白。 批判性地洞察 理解糖蛋白的抗原结构是由以下提供的： 研究它们与单克隆抗体（mAb）的相互作用。 用于 多年来，我们一直在研究流感病毒血凝素（HA） 糖蛋白 这种蛋白质作为其他蛋白质的模型， 类似的功能（例如HIV gp160），而且， 实际上，流感本身就是一种疾病，因为流感仍然是导致 发病率和死亡率。 像许多病毒糖蛋白一样，HA是一种同源寡聚体，由以下组成： 三个相同的单体亚单位。 过去一年，我们继续 研究HA与特定mAb的相互作用， 当HA三聚化时隐藏的抗原位点。 我们发现 这种抗体在体内孵育时能够与三聚体相互作用 温度（37摄氏度）或以上，这种反应性反映了 HA尖端的构象“呼吸”， 抗体进入分子中的一个位置，该位置在 更低的温度。 令人惊讶的是，这种“呼吸”受到了限制， HA中位于分子碱基附近的突变。 这些 研究结果表明，病毒糖蛋白与 保护性抗体可以受到细胞内非常微妙的变化的影响。 病毒蛋白四级结构的动力学。

The improvement of current anti-viral vaccines and the development of novel vaccines depends on increasing our understanding of viral attachment and fusion glycoproteins. Critical insight into understanding the antigenic structure of glycoproteins is provided by studying their interaction with monoclonal antibodies (mAbs). For a number of years we have studied the influenza virus hemagglutinin (HA) glycoprotein. This protein serves as a model for other proteins with similar functions (e.g. HIV gp160), and moreover, is important practically in its own right, as influenza still is a major cause of morbidity and mortality both nationally and internationally. Like many viral glycoproteins the HA is a homo-oligomer, consisting of three identical monomeric subunits. In the past year we continued to investigate the interaction of HA with a particular mAb that recognizes an antigenic site that is hidden when the HA trimerizes. We found that this antibody is able to interact with trimers when incubated at body temperature (37 degrees C) or above, and that this reactivity reflects the conformational "breathing" of the tip of the HA, which allows antibody access to a location in the molecule that is inaccessible at lower temperatures. Surprisingly, this "breathing" was restricted by mutations in the HA located near the base of the molecule. These findings indicate that the interaction of viral glycoproteins with protective antibodies can be influenced by very subtle changes in the dynamics of the quaternary structure of the viral protein.