Stewart, H. orcid.org/0000-0003-1438-1089, Palmulli, R. orcid.org/0000-0003-2271-3186, Johansen, K.H. orcid.org/0000-0002-7711-9451 et al. (12 more authors) (2023) Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release. EMBO reports, 24 (12). ISSN 1469-221X
Abstract
The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We investigate the potential viral proteins involved in abrogating tetherin function and find that SARS-CoV-2 ORF3a reduces tetherin localisation within biosynthetic organelles where Coronaviruses bud, and increases tetherin localisation to late endocytic organelles via reduced retrograde recycling. We also find that expression of Spike protein causes a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS-CoV-2 and highlight the multiple distinct mechanisms by which SARS-CoV-2 subverts tetherin function.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited: https://creativecommons.org/licenses/by/4.0/ |
Keywords: | ORF3a; restriction factor; SARS-CoV-2; spike; tetherin |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Oct 2023 11:05 |
Last Modified: | 25 Oct 2024 15:03 |
Status: | Published |
Publisher: | EMBO |
Refereed: | Yes |
Identification Number: | 10.15252/embr.202357224 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:204268 |