ANTIGENIC AND MOLECULAR CHARACTERIZATION OF THE FUSION GLYCOPROTEIN OF RSV

RSV 融合糖蛋白的抗原和分子特征

• 批准号: 3804806
• 负责人: J A BEELER
• 金额: --
• 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/3804806
• 关键词: Pneumovirus; chimeric proteins; epitope mapping; genetic strain; glycoprotein structure; immunity; molecular cloning; monoclonal antibody; protein structure function; virus cytopathogenic effect; virus protein

Respiratory syncytial virus is the most common cause of lower respiratory tract disease in young children worldwide. The F glycoprotein of this virus is one of the important targets of a protective immune response; however immunity is incomplete and repeated infections occur. Therefore, a major effort of this laboratory has been to construct a detailed epitope map of the RSV F glycoprotein and then evaluate antigenic variation of the F-neutralization and fusion epitopes. The gene for the fusion glycoprotein of the A2 strain of RSV and 14 monoclonal antibody resistant mutants has been cloned and sequenced. Information from over 60 clones has been analyzed in order to identify the amino acids contributing to the epitopes involved in neutralization and fusion. We were successful in determining amino acids that contribute to 5 epitopes in antigenic site A, one epitope in antigenic site AB, 1 epitope in site B and one epitope in site C. Comparison of the deduced amino acid sequence for the monoclonal antibody resistant mutants with F sequences for subgroup A, subgroup B and bovine strains of RSV show that residues involved in most of the site A and C epitopes are conserved among all the strains. This is in contrast to the site B epitope which is located in a hypervariable region. The change in amino acid defined by the site B MARM is likewise changed in the 18537 strain (a subgroup B virus) as well as both bovine strains of RSV. During the next year we propose to evaluate the immune response to RSV F antigenic sites A, B and C following immunization and natural infection.

呼吸道合胞病毒是下呼吸道感染最常见的原因。 在世界范围内的幼儿疾病。 这种F糖蛋白 病毒是保护性免疫反应的重要靶点之一; 然而，免疫是不完全的，反复感染发生。 因此，我们认为， 该实验室的主要努力是构建详细的表位， RSV F糖蛋白的图谱，然后评估RSV F糖蛋白的抗原变异。 F-中和和融合表位。 融合的基因 RSV A_2株糖蛋白和14株单克隆抗体耐药 突变体已被克隆和测序。 来自60多个克隆体的信息 已经进行了分析，以确定氨基酸有助于 参与中和和融合的表位。 我们成功地 确定对抗原位点A中的5个表位有贡献的氨基酸， 一个表位在抗原位点AB，一个表位在位点B，一个表位在 部位C. 单克隆抗体推导的氨基酸序列比较 具有亚组A、亚组B和亚组F序列的抗体抗性突变体 RSV的牛毒株显示，涉及大部分位点A的残基 C抗原表位在所有菌株中是保守的。 这是相对 位于高变区的位点B表位。 的 由位点B MARM定义的氨基酸的变化同样在 18537株（一种亚组B病毒）以及RSV的两种牛株。 在接下来的一年里，我们计划评估对RSV F的免疫应答。 抗原位点A、B和C。