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Volume 105, Issue 1

Mapping respiratory syncytial virus fusion protein interactions with the receptor IGF1R and the impact of alanine-scanning mutagenesis on viral infection Open Access

Abstract

Respiratory syncytial virus (RSV) has two main surface glycoproteins, the attachment glycoprotein (G) and the fusion (F) protein, which together mediate viral entry. Attachment is mediated by the RSV-G protein, while the RSV-F protein makes specific contact with the cellular insulin-like growth factor 1 receptor (IGF1R). This interaction leads to IGF1R activation and initiates a signalling cascade that calls the co-receptor, nucleolin, from the nucleus to the cell surface, where it can trigger viral fusion. We performed molecular docking analysis, which provided a potential set of 35 residues in IGF1R that may be important for interactions with RSV-F. We used alanine-scanning mutagenesis to generate IGF1R mutants and assessed their abundance and maturation, as well as the effect of mutation on RSV infection. We identified several mutations that appear to inhibit IGF1R maturation; but surprisingly, these mutations had no significant effect on RSV infection. This suggests that maturation of IGF1R may not be required for RSV infection. Additionally, we identified one residue, S788, that, when mutated, significantly reduced RSV infection. Further analysis revealed that this mutation disrupted a hydrogen bonding network that may be important for both IGF1R maturation and RSV infection.

  • Received:
  • Accepted:
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Keyword(s): fusion protein , insulin-like growth factor 1 receptor , respiratory syncytial virus and viral entry
Funding
This study was supported by the:
  • Faculty of Medicine, McGill University (Award McGill Interdisciplinary Initiative in Infection and Immunity (MI4))
    • Principle Award Recipient: SelenaM Sagan
  • Institute of Infection and Immunity (Award RN418735)
    • Principle Award Recipient: DavidJ. Marchant
  • Institute of Infection and Immunity (Award RN382934)
    • Principle Award Recipient: DavidJ. Marchant
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-01-17
2024-12-04
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Mapping respiratory syncytial virus fusion protein interactions with the receptor IGF1R and the impact of alanine-scanning mutagenesis on viral infection
J. Gen. Virol. 105, 001951 (2024); https://doi.org/10.1099/jgv.0.001951
/content/journal/jgv/10.1099/jgv.0.001951
/content/journal/jgv/10.1099/jgv.0.001951
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