Abstract
Objective: 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.
Methods: 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).
Results: 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.
Conclusion: SARS-CoV-2 S protein enhances ACE2 expression via facilitating IFN effects, which may help its infection.
Keywords: ACE2; Interferon; SARS-CoV-2; Spike.
【저자키워드】 SARS-CoV-2, ACE2, interferon, Spike., 【초록키워드】 Transcriptome, Antiviral, S protein, spike, qRT-PCR, Infection, interferon, SARS-CoV-2 receptor, non-structural proteins, Protein, RNA-Seq, western blot, Phosphorylation, non-structural protein, IFN, Stat1, ACE2 expression, expression, transcriptome analysis, ISGs, ISG, association, Interaction, STAT, ISG15, Analysis, epithelial cell, Activation, STAT2, help, JAK1, SARS-CoV-2 S, receptor ACE2, overexpression, co-immunoprecipitation, upstream, co-IP, downstream, BEAS-2B, Host, Effect, Effects, ENhance, Beas-2B cells, identify, was performed, promote, activate, epithelial cell line, Type, overexpressed, were measured, BEAS-2B cell, JAK-STAT signaling, the SARS-CoV-2, 【제목키워드】 spike, Protein, Bronchial epithelium, Effect, ENhance,