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.
Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Bronchi/drug effects , COVID-19/virology , Epithelial Cells/drug effects , Interferon alpha-2/pharmacology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/genetics , Bronchi/enzymology , Bronchi/virology , COVID-19/enzymology , Cytokines/genetics , Cytokines/metabolism , Epithelial Cells/enzymology , Epithelial Cells/virology , HEK293 Cells , Host-Pathogen Interactions , Humans , Janus Kinase 1/metabolism , Phosphorylation , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , STAT1 Transcription Factor/metabolism , STAT2 Transcription Factor/metabolism , Signal Transduction , Spike Glycoprotein, Coronavirus/genetics , Ubiquitins/genetics , Ubiquitins/metabolism , Up-RegulationABSTRACT
OBJECTIVES: The aim of this study was to investigate risk factors and psychological stress of health-care workers (HCWs) with coronavirus disease 2019 (COVID-19) in a nonfrontline clinical department. METHODS: Data of 2 source patients and all HCWs with infection risk were obtained in a department in Wuhan from January to February 2020. A questionnaire was designed to evaluate psychological stress of COVID-19 on HCWs. RESULTS: The overall infection rate was 4.8% in HCWs. Ten of 25 HCWs who contacted with 2 source patients were diagnosed with confirmed COVID-19 (8/10) and suspected COVID-19 (2/10). Other 2 HCWs were transmitted by other patients or colleagues. Close care behaviors included physical examination (6/12), life nursing (4/12), ward rounds (4/12), endoscopic examination (2/12). Contacts fluctuated from 1 to 24 times and each contact was short (8.1 min ± 5.6 min). HCWs wore surgical masks (11/12), gloves (7/12), and isolation clothing (3/12) when providing medical care. Most HCWs experienced a mild course with 2 asymptomatic infections, taking 9.8 d and 20.9 d to obtain viral shedding and clinical cure, respectively. Psychological stress included worry (58.3%), anxiety (83.3%), depression (58.3%), and insomnia (58.3%). CONCLUSIONS: Close contact with COVID-19 patients and insufficient protection were key risk factors. Precaution measures and psychological support on COVID-19 is urgently required for HCWs.