Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most important emerging pathogen worldwide, but its early transcriptional dynamics and host immune response remain unclear. Herein, the expression profiles of viral interactions with different types of hosts were comprehen...

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Autores principales: Lijia Jia, Zhen Chen, Yecheng Zhang, Li Ma, Liying Wang, Xiao Hu, Haizhou Liu, Jianjun Chen, Di Liu, Wuxiang Guan
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/57e3f3e4c4054aa9bd4e5c31dec4aa4b
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spelling oai:doaj.org-article:57e3f3e4c4054aa9bd4e5c31dec4aa4b2021-12-01T07:00:08ZSuppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection1664-302X10.3389/fmicb.2021.768740https://doaj.org/article/57e3f3e4c4054aa9bd4e5c31dec4aa4b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.768740/fullhttps://doaj.org/toc/1664-302XSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most important emerging pathogen worldwide, but its early transcriptional dynamics and host immune response remain unclear. Herein, the expression profiles of viral interactions with different types of hosts were comprehensively dissected to shed light on the early infection strategy of SARS-CoV-2 and the host immune response against infection. SARS-CoV-2 was found to exhibit a two-stage transcriptional strategy within the first 24 h of infection, comprising a lag phase that ends with the virus being paused and a log phase that starts when the viral load increases rapidly. Interestingly, the host innate immune response was found not to be activated (latent period) until the virus entered the log stage. Noteworthy, when intracellular immunity is suppressed, SARS-CoV-2 shows a correlation with dysregulation of metal ion homeostasis. Herein, the inhibitory activity of copper ions against SARS-CoV-2 was further validated in in vitro experiments. Coronavirus disease 2019-related genes (including CD38, PTX3, and TCN1) were also identified, which may serve as candidate host-restricted factors for interventional therapy. Collectively, these results confirm that the two-stage strategy of SARS-CoV-2 effectively aids its survival in early infection by regulating the host intracellular immunity, highlighting the key role of interferon in viral infection and potential therapeutic candidates for further investigations on antiviral strategies.Lijia JiaLijia JiaZhen ChenYecheng ZhangYecheng ZhangLi MaLi MaLiying WangLiying WangXiao HuXiao HuHaizhou LiuJianjun ChenDi LiuDi LiuWuxiang GuanFrontiers Media S.A.articleSARS-CoV-2transcriptional dynamicsinterferon responsehost restriction factorsvirus-host interactionsMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic SARS-CoV-2
transcriptional dynamics
interferon response
host restriction factors
virus-host interactions
Microbiology
QR1-502
spellingShingle SARS-CoV-2
transcriptional dynamics
interferon response
host restriction factors
virus-host interactions
Microbiology
QR1-502
Lijia Jia
Lijia Jia
Zhen Chen
Yecheng Zhang
Yecheng Zhang
Li Ma
Li Ma
Liying Wang
Liying Wang
Xiao Hu
Xiao Hu
Haizhou Liu
Jianjun Chen
Di Liu
Di Liu
Wuxiang Guan
Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most important emerging pathogen worldwide, but its early transcriptional dynamics and host immune response remain unclear. Herein, the expression profiles of viral interactions with different types of hosts were comprehensively dissected to shed light on the early infection strategy of SARS-CoV-2 and the host immune response against infection. SARS-CoV-2 was found to exhibit a two-stage transcriptional strategy within the first 24 h of infection, comprising a lag phase that ends with the virus being paused and a log phase that starts when the viral load increases rapidly. Interestingly, the host innate immune response was found not to be activated (latent period) until the virus entered the log stage. Noteworthy, when intracellular immunity is suppressed, SARS-CoV-2 shows a correlation with dysregulation of metal ion homeostasis. Herein, the inhibitory activity of copper ions against SARS-CoV-2 was further validated in in vitro experiments. Coronavirus disease 2019-related genes (including CD38, PTX3, and TCN1) were also identified, which may serve as candidate host-restricted factors for interventional therapy. Collectively, these results confirm that the two-stage strategy of SARS-CoV-2 effectively aids its survival in early infection by regulating the host intracellular immunity, highlighting the key role of interferon in viral infection and potential therapeutic candidates for further investigations on antiviral strategies.
format article
author Lijia Jia
Lijia Jia
Zhen Chen
Yecheng Zhang
Yecheng Zhang
Li Ma
Li Ma
Liying Wang
Liying Wang
Xiao Hu
Xiao Hu
Haizhou Liu
Jianjun Chen
Di Liu
Di Liu
Wuxiang Guan
author_facet Lijia Jia
Lijia Jia
Zhen Chen
Yecheng Zhang
Yecheng Zhang
Li Ma
Li Ma
Liying Wang
Liying Wang
Xiao Hu
Xiao Hu
Haizhou Liu
Jianjun Chen
Di Liu
Di Liu
Wuxiang Guan
author_sort Lijia Jia
title Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection
title_short Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection
title_full Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection
title_fullStr Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection
title_full_unstemmed Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection
title_sort suppression and activation of intracellular immune response in initial severe acute respiratory syndrome coronavirus 2 infection
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/57e3f3e4c4054aa9bd4e5c31dec4aa4b
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