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

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 ov...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Federation of Immunological Societies. Published by Elsevier B.V. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254647/
https://www.ncbi.nlm.nih.gov/pubmed/34228987
http://dx.doi.org/10.1016/j.imlet.2021.06.008
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author 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
author_facet 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
author_sort Zhou, Ye
collection PubMed
description 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.
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spelling pubmed-82546472021-07-06 SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium 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 Immunol Lett Article 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. European Federation of Immunological Societies. Published by Elsevier B.V. 2021-09 2021-07-03 /pmc/articles/PMC8254647/ /pubmed/34228987 http://dx.doi.org/10.1016/j.imlet.2021.06.008 Text en © 2021 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
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
SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium
title SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium
title_full SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium
title_fullStr SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium
title_full_unstemmed SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium
title_short SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium
title_sort sars-cov-2 spike protein enhances ace2 expression via facilitating interferon effects in bronchial epithelium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254647/
https://www.ncbi.nlm.nih.gov/pubmed/34228987
http://dx.doi.org/10.1016/j.imlet.2021.06.008
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