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

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Conley, Michaela J., Short, Judith M., Burns, Andrew M., Streetley, James, Hutchings, Joshua, Bakker, Saskia, Power, B. Joanne, Jaffery, Hussain, Haney, Joanne, Zanetti, Giulia, Murcia, Pablo R., Stewart, Murray, Fearns, Rachel, Vijayakrishnan, Swetha and Bhella, David (2022) Helical ordering of envelope‐associated proteins and glycoproteins in respiratory syncytial virus. The EMBO Journal, 41 (3). e109728. doi:10.15252/embj.2021109728 ISSN 0261-4189.

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Official URL: http://dx.doi.org/10.15252/embj.2021109728

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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: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
Q Science > QR Microbiology
R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Respiratory syncytial virus, Cryomicroscopy, Electron microscopy, Tomography, Respiratory syncytial virus -- Infections -- Tomography, Glycoproteins , Extracellular matrix proteins, Virus-vector relationships
Journal or Publication Title: The EMBO Journal
Publisher: Nature Publishing Group
ISSN: 0261-4189
Official Date: February 2022
Dates:
DateEvent
February 2022Published
1 December 2021Available
3 December 2021Accepted
Volume: 41
Number: 3
Article Number: e109728
DOI: 10.15252/embj.2021109728
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 9 February 2022
Date of first compliant Open Access: 10 February 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
EM16637-5Wellcome Trusthttp://dx.doi.org/10.13039/100010269
EM16637-5[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
EM16637-5[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
MC_UU_12014/7 [MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/M000451/1 [MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_12014/9 [MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC-A025-5PL41 [MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
1R01AI113321National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
102463/Z/13/Z Wellcome Trusthttp://dx.doi.org/10.13039/100010269
099786/Z/12/Z Wellcome Trusthttp://dx.doi.org/10.13039/100010269

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