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Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release

Stewart, Hazel; Palmulli, Roberta; Johansen, Kristoffer H; McGovern, Naomi; Shehata, Ola M; Carnell, George W; Jackson, Hannah K; ... Edgar, James R; + view all (2023) Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release. EMBO Reports , Article e57224. 10.15252/embr.202357224. Green open access

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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.

Type: Article
Title: Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embr.202357224
Publisher version: https://doi.org/10.15252/embr.202357224
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: ORF3a; restriction factor; SARS-CoV-2; spike; tetherin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10179016
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