Unveiling the key defender: PLSCR1 identified as a potent anti-SARS-CoV-2 factor in COVID-19 immunity Nature covid COVID19 SARSCoV2 defender defence immunity
By Neha MathurJul 14 2023Reviewed by Lily Ramsey, LLM In a recent study published in Nature, researchers identified the anti-severe acute respiratory syndrome coronavirus 2 function of phospholipid scramblase 1 , a cell-autonomous restriction factor induced by interferon-gamma .
Background In many plants, bacteria, and animals, including humans, cell-autonomous immunity helps combat viral and other infections, e.g., Shigella flexneri and Mycobacterium tuberculosis. IFNγ, a type II cytokine, is a well-recognized agent of mobilization of cell-autonomous immunity in most nucleated cells.
About the study In the present study, researchers used human Huh7.5 hepatoma and A549-ACE2 cells to test IFNγ potency in restricting live SARS-CoV-2 infection, which they confirmed using CRISPR–Cas9 engineering. In addition, the team identified PLSCR1 identified which step of the SARS-CoV-2 life cycle and how it blocked coronavirus invasion via a cathepsin-dependent endosomal fusion pathway or transmembrane serine protease 2 -dependent cell-surface fusion pathway.
Third, in PLSCR1-knockout cells, SARS-CoV-2 spike-mediated cell–cell fusion increased significantly, while PLSCR1 overexpression reduced this response. These observations confirmed that PLSCR1 directly prevented membrane fusion triggered by the SARS-CoV-2 S protein.
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