Cell Signal. 2021 Jun 17
Yinfang Wang, Yingzhe Fan, Yitong Huang,Tao Du, Zongjun Liu, Dekui Huang, Ying Wang, Nanping Wang, and Peng Zhang
Products used in the paper Details Operation
SARS-CoV-2 spike-pseudotyped lentivirus The SARS-CoV-2 spike-pseudotyped lentivirus that containing expression cassettes for firefly luciferase instead of the VSV-G open reading frame (LV-Spike-nCoV-Luc) was purchased from PackGene Biotech (Guangzhou, China). Request Quote

Research Field: Covid-related

AAV Serotype: SARS-CoV-2, Lung epithelial cells, NK cells, TRIM28, ACE2, IFN-γ receptor


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. The expression level of ACE2 potentially determine the susceptibility and severity of COVID-19, it is thus of importance to understand the regulatory mechanism of ACE2 expression. Tripartite motif containing 28 (TRIM28) is known to be involved in multiple processes including antiviral restriction, endogenous retrovirus latency and immune response, it is recently reported to be co-expressed with SARS-CoV-2 receptor in type II pneumocytes; however, the roles of TRIM28 in ACE2 expression and SARS-CoV-2 cell entry remain unclear. This study showed that knockdown of TRIM28 induces ACE2 expression and increases pseudotyped SARS-CoV-2 cell entry of A549 cells and primary pulmonary alveolar epithelial cells (PAEpiCs). In a co-culture model of NK cells and lung epithelial cells, our results demonstrated that NK cells inhibit TRIM28 and promote ACE2 expression in lung epithelial cells, which was partially reversed by depletion of interleukin-2 and blocking of granzyme B in the co-culture medium. 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. The upregulated ACE2 induced by TRIM28 knockdown and co-culture of NK cells was partially reversed by dexamethasone in A549 cells. Our study identified TRIM28 as a novel regulator of ACE2 expression and SARS-CoV-2 cell entry.

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