Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation

• DOI: 10.1038/s42003-022-03609-0
• Publication Date: 2022-07-01T17:09:05Z
• Authors: Xiaoming Hu; Yuguo Niu; Peixiang Luo; Fei Xiao; Feixiang Yuan; Hanrui Yin; Shanghai Chen; Feifan Guo
• Keywords: Angiotensin-converting enzyme 2

Abstract Angiotensin-converting enzyme 2 (ACE2) has been identified as a primary receptor for severe acute respiratory syndrome coronaviruses (SARS-CoV-2). Here, we investigated the expression regulation of ACE2 in enterocytes under amino acid deprivation conditions. In this study, found that was upregulated upon all or single essential human colonic epithelial CCD841 cells. Furthermore, knockdown general control nonderepressible ( GCN2 ) reduced intestinal mRNA and protein levels vitro vivo. Consistently, revealed two inhibitors, GCN2iB GCN2-IN-1, downregulated Moreover, increased response to leucine dependent. Through RNA-sequencing analysis, transcription factors, MAFB MAFF, positively regulated These findings demonstrate deficiency increases thereby likely aggravates SARS-CoV-2 infection.