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: 3811254
• 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/3811254
• 关键词: Pneumovirus; antibody formation; chimeric proteins; epitope mapping; glycoprotein structure; immunity; laboratory rat; molecular biology; molecular cloning; polymerase chain reaction; protein structure function; virus cytopathogenic effect; virus replication

Respiratory syncytial virus is the common cause of lower respiratory tract diseases in infancy. The F glycoprotein of this virus has been identified as 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 evaluate antigenic variation of the neutralization and fusion epitopes and construct a detailed molecular epitope map of RSV F. The genes for the fusion glycoprotein of RSV-F monoclonal antibody resistant mutants have been cloned and sequenced. Briefly, a cDNA copy of viral mRNA was amplified by polymerase chain reaction and cloned into M13. Sequence analysis has identified the amino acid residues in the neutralization epitopes of antigenic sites A, B, and C. The most dramatic substitution results in a change in charge in a site A epitope and Garnier analysis predicts a significant alteration in the secondary structure of the F glycoprotein. Consistent with these findings, variants that contain this change exhibit a small plaque phenotype, suggesting that a decrease in function has occurred as a result of a modification in the structure of the F glycoprotein. We also compared replication of these viruses in the cotton rat. Several of the variant viruses, including those with a small plaque phenotype, had a decreased ability to replicate in cotton rat lungs when compared to the parent virus. This suggests that the F glycoprotein may be one of the determinants of virulence and cellular tropism in vivo. Furthermore, naturally occurring attenuated strains may exist and play a role in the development of a complete o I partial protective immune response. Studies are under way to more completely characterize RSV-F from these variant viruses and to further evaluate the antibody response to this glycoprotein.

呼吸道合胞病毒是下呼吸道的常见病因