FOLDING, ASSEMBLY, AND TRANSPORT OF VIRAL GLYCOPROTEINS

病毒糖蛋白的折叠、组装和运输

• 批准号: 5200499
• 负责人: J W YEWDELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/5200499
• 关键词: Golgi apparatus; HIV envelope protein gp160; Orthomyxoviridae; endoplasmic reticulum; fluorescence microscopy; glycoproteins; immunocytochemistry; influenzavirus A; inhibitor /antagonist; intracellular transport; microorganism hemagglutinin; monoclonal antibody; polymerization; protein biosynthesis; protein folding; protein structure; protein transport; virus protein

The improvement of current antiviral 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 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 site of trimerization of newly synthesized HA. Our previously published findings suggested that HA trimerization occurs only after monomers are exported from the ER. In the past year we have used a number of novel inhibitors of ER to Golgi complex traffic to demonstrate immunocytochemically and biochemically that trimerization occurs in the ERGIC (acronymic for ER- Golgi Intermediate Compartment).

现有抗病毒疫苗的改进和抗病毒药物的开发 新型疫苗取决于我们对病毒的了解 附着和融合糖蛋白。 对理解的批判性洞察 通过研究糖蛋白的抗原结构， 与单克隆抗体（mAb）的相互作用。 多年来，我们 研究了流感病毒血凝素（HA）糖蛋白。 这 蛋白质作为具有类似功能的其他蛋白质的模型 (e.g., HIV gp 160），而且，它本身在实践中也很重要。 对，因为流感仍然是发病率和死亡率的主要原因， 在国内和国际上。 与许多病毒糖蛋白一样， 是由三个相同的单体亚基组成的同源寡聚体。 在过去的一年里，我们继续研究三聚体的位置， 新合成的HA。 我们先前发表的研究结果表明， HA三聚化仅在单体从聚合物中输出后发生， 儿 在过去的一年里，我们已经使用了一些新的ER抑制剂， 高尔基复合体的运输，以证明免疫细胞化学和 在生物化学上，三聚化发生在ERGIC（ER-的首字母缩写）中。 Golgi Intermediate combinant）。