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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Frontiers Media S.A.
2021
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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 |
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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 |
work_keys_str_mv |
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