| Autor: |
Hayes RS; Department of Biochemistry, McGill University, Montreal, Canada., Oraby AK; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.; Department of Pharmaceutical Organic Chemistry, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Al-Motamayez District, 6th of October City, Giza, Egypt., Camargo C; Department of Microbiology and Immunology, McGill University, Montreal, Canada.; Department of Microbiology and Immunology, The University of British Columbia, Vancouver, Canada., Marchant DJ; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada., Sagan SM; Department of Biochemistry, McGill University, Montreal, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, Canada.; Department of Microbiology and Immunology, The University of British Columbia, Vancouver, Canada. |
| Abstrakt: |
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. |
