SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium.
SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium.
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SARS-CoV-2 刺突蛋白通过促进支气管上皮中的干扰素效应来增强 ACE2 表达。
DOI：
10.1016/j.imlet.2021.06.008
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发表时间：
2021-09
影响因子：
4.4
通讯作者：
Hou J
中科院分区：
文献类型：
--
作者：
Zhou Y;Wang M;Li Y;Wang P;Zhao P;Yang Z;Wang S;Zhang L;Li Z;Jia K;Zhong C;Li N;Yu Y;Hou J
本研究旨在探讨SARS冠状病毒2型（SARS-CoV-2）与宿主I型干扰素（IFN）反应的相互作用，以确定SARS冠状病毒2型（SARS-CoV-2）产物是否影响IFN的作用。将SARS-CoV-2的所有结构蛋白和非结构蛋白分别转染支气管上皮细胞BEAS-2B并过表达，qRT-PCR检测典型抗病毒干扰素刺激基因（ISG）ISG 15的表达。在对照和Spike（S）蛋白过表达的BEAS-2B细胞之间进行基于RNA-seq的转录组分析。通过qRT-PCR和/或Western blot分别检测对照和S蛋白过表达的BEAS-2B细胞中ACE 2的表达和IFN效应因子JAK-STAT信号通路的激活。在BEAS-2B细胞中，通过免疫共沉淀（co-IP）来测量S蛋白与STAT 1和STAT 2之间的相互作用以及JAK 1与下游STAT 1和STAT 2之间的关联。S蛋白可激活IFN效应和下游ISGs的表达。通过转录组分析，S蛋白的过表达诱导了一系列基因的表达，包括一系列ISG和SARS-CoV-2受体ACE 2。在机制上，S蛋白增强了上游JAK 1与下游STAT 1和STAT 2之间的结合，从而促进了STAT 1和STAT 2的磷酸化和ACE 2的表达。SARS-CoV-2S蛋白通过促进IFN效应而增强ACE 2的表达，这可能有助于其感染。
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.
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DOI：
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发表时间：
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期刊：
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影响因子：
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