TRIM28 Regulates SARS-CoV-2 Cell Entry by Targeting ACE2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019, it binds to angiotensin-converting enzyme 2 (ACE2) to enter into human cells. This study showed that knockdown of Tripartite motif containing 28 (TRIM28) induces ACE2 expression and increases pseudotyped SARS-CoV-2 cell entry of A549 cells and primary pulmonary alveolar epithelial cells (PAEpiCs). Natural killer (NK) cell-derived factors can inhibit TRIM28 and promote ACE2 expression in lung epithelial cells, which was partially reversed by depletion of interleukin-2 and blocking of granzyme B. Furthermore, TRIM28 knockdown enhanced interferon-γ (IFN-γ)-induced ACE2 expression through a mechanism involving upregulating IFN-γ receptor 2 (IFNGR2) in both A549 and PAEpiCs. Importantly, the upregulated ACE2 induced by TRIM28 knockdown and co-culture of NK cells was partially reversed by dexamethasone in A549 cells but not PAEpiCs. This study identified TRIM28 as a regulator of ACE2 expression and SARS-CoV-2 cell entry.Funding: This study was supported by the National Natural Science Foundation of China (81870327, 81770443) and Clinical Advantage Discipline of Health System of Putuo District in Shanghai (#ptkwws201901 and #2019ysxk01).Conflict of Interest: The authors declare no competing interests.