Conley, M. J. et al. (2022) Helical ordering of envelope associated proteins and glycoproteins in respiratory syncytial virus. EMBO Journal, 41(3), e109728. (doi: 10.15252/embj.2021109728) (PMID:34935163) (PMCID:PMC8804925)
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Abstract
Human respiratory syncytial virus (RSV) causes severe respiratory illness in children and the elderly. Here, using cryogenic electron microscopy and tomography combined with computational image analysis and three-dimensional reconstruction, we show that there is extensive helical ordering of the envelope-associated proteins and glycoproteins of RSV filamentous virions. We calculated a 16 Å resolution sub-tomogram average of the matrix protein (M) layer that forms an endoskeleton below the viral envelope. These data define a helical lattice of M-dimers, showing how M is oriented relative to the viral envelope. Glycoproteins that stud the viral envelope were also found to be helically ordered, a property that was coordinated by the M-layer. Furthermore, envelope glycoproteins clustered in pairs, a feature that may have implications for the conformation of fusion (F) glycoprotein epitopes that are the principal target for vaccine and monoclonal antibody development. We also report the presence, in authentic virus infections, of N-RNA rings packaged within RSV virions. These data provide molecular insight into the organisation of the virion and the mechanism of its assembly.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the United Kingdom Medical Research Council (MC_UU_12014/7 to DB; MR/M000451/1 to DB, RF, MJC, JS and SEB; MC_UU_12014/9 to PRM and JH; MC-A025-5PL41 to MS). RF, DB and AMB were supported by the United States of America National Institutes of Health (1R01AI113321), BJP and HJ were supported by a Wellcome doctoral training programme (102463/Z/13/Z and 099786/Z/12/Z respectively). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Burns, Andrew and Streetley, Dr James and Haney, Ms Joanne and Conley, Dr Michaela and Bakker, Dr Saskia and Hutchings, Dr Joshua and Jaffery, Dr Hussain and Bhella, Professor David and Vijayakrishnan, Dr Swetha and Murcia, Professor Pablo |
| Creator Roles: | Conley, M.Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing Burns, A.Investigation Streetley, J.Investigation, Writing – review and editing Hutchings, J.Formal analysis, Methodology, Writing – review and editing Bakker, S.Investigation, Supervision, Writing – review and editing Jaffery, H.Investigation Haney, J.Investigation Murcia, P.Conceptualization, Funding acquisition Vijayakrishnan, S.Investigation, Methodology, Supervision, Writing – review and editing Bhella, D.Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Visualization, Writing – original draft, Writing – review and editing |
| Authors: | Conley, M. J., Short, J. M., Burns, A. M., Streetley, J., Hutchings, J., Bakker, S. E., Power, B. J., Jaffery, H., Haney, J., Zanetti, G., Murcia, P. R., Stewart, M., Fearns, R., Vijayakrishnan, S., and Bhella, D. |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | EMBO Journal |
| Publisher: | EMBO Press |
| ISSN: | 0261-4189 |
| ISSN (Online): | 1460-2075 |
| Published Online: | 22 December 2021 |
| Copyright Holders: | Copyright © 2021 The Authors |
| First Published: | First published in EMBO Journal 41(3): e109728 |
| Publisher Policy: | Reproduced under a Creative Commons Licence |
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