Helical ordering of envelope associated proteins and glycoproteins in respiratory syncytial virus

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:Hutchings, Dr Joshua and Burns, Andrew and Jaffery, Dr Hussain and Streetley, Dr James and Haney, Ms Joanne and Conley, Dr Michaela and Bhella, Professor David and Bakker, Dr Saskia 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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656541Structural studies of human viruses and host interactionsDavid BhellaMedical Research Council (MRC)MC_UU_12014/7MVLS III - CENTRE FOR VIRUS RESEARCH
190802A structure analysis of the intact virion and replicative complexes of human respiratory syncytial virusDavid BhellaMedical Research Council (MRC)MR/M000451/1III-MRC-GU Centre for Virus Research
172630Quinquennial Core FundsMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/9III-MRC-GU CVR Support Services
171960Initiation and regulation of RSV mRNA transcription and genome replicationDavid BhellaNational Institute of Allergy and Infectious Diseases (NIAID)1R01AI113321-01III-MRC-GU Centre for Virus Research
168512Molecular Functions in Disease PhD Programme (2013-2017)Darren MoncktonWellcome Trust (WELLCOTR)102463/Z/13/ZMCSB - Molecular Genetics
166999Molecular Functions in Disease (PhD Studentship 2012-2016)Darren MoncktonWellcome Trust (WELLCOTR)099786/Z/12/ZMCSB - Molecular Genetics