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

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