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

Hisao Okabe; Koichi Hashimoto; Sakurako Norito; Yuichiro Asano; Masatoki Sato; Yohei Kume; Mina Chishiki; Hajime Maeda; Fumi Mashiyama; Aya Takeyama; Hiromichi Murai; Kenji Nemoto; Masaki Ito; Shigeo Suzuki; Hiroko Sakuma; Kazuya Shirato; Hayato Go; Mitsuaki Hosoya

doi:10.1093/infdis/jiae636

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

J Infect Dis. 2024 Dec 24:jiae636. doi: 10.1093/infdis/jiae636. Online ahead of print.

Authors

Hisao Okabe¹, Koichi Hashimoto¹, Sakurako Norito¹, Yuichiro Asano¹, Masatoki Sato¹, Yohei Kume¹, Mina Chishiki¹, Hajime Maeda¹, Fumi Mashiyama², Aya Takeyama³, Hiromichi Murai⁴, Kenji Nemoto⁴, Masaki Ito³, Shigeo Suzuki⁵, Hiroko Sakuma², Kazuya Shirato⁶, Hayato Go¹, Mitsuaki Hosoya¹

Affiliations

¹ Department of Pediatrics, School of Medicine, Fukushima Medical University, Fukushima City, Fukushima 960-1295, Japan.
² Department of Pediatrics, Hoshi General Hospital, Koriyama City, Fukushima 963-8801, Japan.
³ Department of Pediatrics, Soma General Hospital, Soma City, Fukushima 976-0011, Japan.
⁴ Department of Pediatrics, Shirakawa Kosei General Hospital, Shirakawa City, Fukushima 961-0005, Japan.
⁵ Department of Pediatrics, d Department of Pediatrics, Shirakawa Kosei General Hospital, Shirakawa City, Fukushima 961-0005, Japan, Fukushima City, Fukushima 960-8101, Japan.
⁶ Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.

PMID: 39719011
DOI: 10.1093/infdis/jiae636

Abstract

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.

Keywords: Fukushima; Japan; amino acid substitution; fusion protein; monoclonal antibody; replicative ability; respiratory syncytial virus; susceptibility.

Plain language summary

Recent predominant strains of respiratory syncytial virus subtype B have amino acid substitutions in the F protein: L172Q/S173L, decreasing susceptibility to suptavumab (antibody against site Ⅴ), and I206M/Q209R, increasing susceptibility to nirsevimab (antibody against site Ø) and replicative ability.

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