A single amino acid mutation alters multiple neutralization epitopes in the respiratory syncytial virus fusion glycoprotein.

ABSTRACT: Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization. All current RSV therapeutics, including antibody prophylaxis and adult vaccination, target the RSV fusion glycoprotein (RSV-F). The seven neutralization sites on RSV-F are highly conserved and infrequently mutate. Here, we show that a single amino acid mutation at position 305 in RSV-F significantly alters antigenic recognition of RSV-F binding sites and reduces the susceptibility of RSV to neutralizing antibodies. In an in vitro evolution assay, we show that RSV-F L305I occurs in a majority of RSV quasi-species. Computational modeling predicted that the L305I mutation altered the epitope landscape of RSV-F, resulting in changes to neutralizing antibody sensitivity and affinity towards the RSV-F glycoprotein.

SUBMITTER: Oraby AK 

PROVIDER: S-EPMC12015481 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature