SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium

• Published in: Immunology letters 2021-09, Vol.237, p.33-41
• Main Authors: Zhou, Ye, Wang, Mu, Li, Yunhui, Wang, Peihui, Zhao, Ping, Yang, Zixuan, Wang, Suyuan, Zhang, Liyuan, Li, Zhenyang, Jia, Kaiwei, Zhong, Cuiping, Li, Nan, Yu, Yizhi, Hou, Jin
• Format: Article
• Language: English
• Subjects: ACE2; Interferon; SARS-CoV-2; Spike
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/j.imlet.2021.06.008

•SARS-CoV-2 Spike protein increases ISGs expression•SARS-CoV-2 Spike protein enhances its receptor ACE2 expression•Spike protein enhances ACE2 expression by activating IFN effector signaling•Spike protein activates STAT1 and STAT2 via promoting their association with JAK1 In this study, we focused on the interaction between SARS-CoV-2 and host Type I Interferon (IFN) response, so as to identify whether IFN effects could be influenced by the products of SARS-CoV-2. All the structural and non-structural proteins of SARS-CoV-2 were transfected and overexpressed in the bronchial epithelial cell line BEAS-2B respectively, and typical antiviral IFN-stimulated gene (ISG) ISG15 expression was detected by qRT-PCR. RNA-seq based transcriptome analysis was performed between control and Spike (S) protein-overexpressed BEAS-2B cells. The expression of ACE2 and IFN effector JAK-STAT signaling activation were detected in control and S protein-overexpressed BEAS-2B cells by qRT-PCR or/and Western blot respectively. The interaction between S protein with STAT1 and STAT2, and the association between JAK1 with downstream STAT1 and STAT2 were measured in BEAS-2B cells by co-immunoprecipitation (co-IP). S protein could activate IFN effects and downstream ISGs expression. By transcriptome analysis, overexpression of S protein induced a set of genes expression, including series of ISGs and the SARS-CoV-2 receptor ACE2. Mechanistically, S protein enhanced the association between the upstream JAK1 and downstream STAT1 and STAT2, so as to promote STAT1 and STAT2 phosphorylation and ACE2 expression. SARS-CoV-2 S protein enhances ACE2 expression via facilitating IFN effects, which may help its infection.