Amino acid substitutions in the fusion protein of respiratory syncytial virus in Fukushima, Japan during 2008-2023 and their effects.

Background: Amino acid (AA) substitutions in the fusion protein of respiratory syncytial virus (RSV) and their effects remain unclear. We aimed to analyze AA substitutions in main neutralizing epitopes of the fusion (F) protein.

Methods: We analyzed F protein genes of 236 RSV strains isolated from children hospitalized with RSV infection in Fukushima, Japan (June 2008-February 2023). AA substitutions were detected at antigenic sites II, V, and Ø, the main neutralizing epitopes. We conducted neutralization assays using site-specific mAbs to investigate the relationship between AA substitutions and mAb susceptibility. Finally, we examined viral replicative ability.

Results: Site Ⅱ: RSV strains isolated from children receiving palivizumab treatment exhibited the K272M substitution in RSV-A and K272E substitution in RSV-B, showing reduced susceptibility to site Ⅱ-specific antibody. Site Ⅴ: In RSV-A, >50% of strains isolated since 2022 harbored the V178I substitution; however, this did not change susceptibility to site Ⅴ-specific antibody. In RSV-B, L172Q/S173L mutant strains became predominant around 2016, leading to reduced susceptibility to site Ⅴ-specific antibodies. Site Ø: No AA substitutions were detected in RSV-A. In RSV-B, the I206M/Q209R mutant strain became predominant around 2018, leading to improved site Ø-specific antibody susceptibility and replicative ability. However, none of the substitutions reduced susceptibility to site Ø-specific antibodies.

Conclusions: The RSV F protein in Fukushima has naturally undergone AA substitutions with corresponding changes in antibody susceptibility. In addition to substitutions similar to those observed globally, unique substitutions have been observed. Therefore, AA substitutions and antibody susceptibility in various regions must be monitored.