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.
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.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- ACE2
- angiotensin converting enzyme 2
- Bst2
- bone marrow stromal antigen 2
- DMV
- double membrane vesicle
- ERGIC
- endoplasmic reticulum-Golgi intermediate compartments
- GPI
- glycosylphosphatidylinositol
- IFN
- interferon
- LAMP1
- Lysosomal-associated membrane protein 1
- SARS
- severe acute respiratory syndrome.
