Dataset Information

SARS-CoV-2 spike downregulates tetherin to enhance viral spread.

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 downregulates tetherin to aid its release from cells, and investigate potential proteins involved in this process. Loss of tetherin from cells caused an increase in SARS-CoV-2 viral titre. We find SARS-CoV-2 spike protein to be responsible for tetherin downregulation, rather than ORF7a as previously described for the 2002-2003 SARS-CoV. We instead find ORF7a to be responsible for Golgi fragmentation, and expression of ORF7a in cells recapitulates Golgi fragmentation observed in SARS-CoV-2 infected cells.

Highlights

SARS-CoV-2 downregulates the host restriction factor, tetherin.Tetherin loss enhances viral titre and spread.SARS-CoV-2 ORF7a protein does not downregulate tetherin, but instead induces Golgi fragmentation.Tetherin downregulation is mediated by SARS-CoV-2 spike.

SUBMITTER: Stewart H

PROVIDER: S-EPMC7805449 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Tetherin antagonism by SARS-CoV-2 enhances virus release: multiple mechanisms including ORF3a-mediated defective retrograde traffic.

Stewart Hazel H Palmulli Roberta R Johansen Kristoffer H KH McGovern Naomi N Shehata Ola M OM Carnell George W GW Jackson Hannah K HK Lee Jin S JS Brown Jonathan C JC Burgoyne Thomas T Burgoyne Thomas T Heeney Jonathan L JL Okkenhaug Klaus K Firth Andrew E AE Peden Andrew A AA Edgar James R JR

bioRxiv : the preprint server for biology 20221222

The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the <i>Coronaviridae</i>. 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 demonstrated that SARS-CoV-2 infection causes tetherin downregulation, and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We inve ...[more]

PMID: 33442692

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