Comparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses

Abstract The transcriptome of SARS-CoV-2-infected cells that reflects the interplay between host and virus has provided valuable insights into mechanisms underlying SARS-CoV-2 infection and COVID-19 disease progression. In this study, we show that SARS-CoV-2 can establish a robust infection in HEK29...

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Autores principales: Guihua Sun, Qi Cui, Gustavo Garcia, Cheng Wang, Mingzi Zhang, Vaithilingaraja Arumugaswami, Arthur D. Riggs, Yanhong Shi
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/0f087bf8808a4cf993b837bd93dab18a
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spelling oai:doaj.org-article:0f087bf8808a4cf993b837bd93dab18a2021-12-02T19:02:40ZComparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses10.1038/s41598-021-96462-w2045-2322https://doaj.org/article/0f087bf8808a4cf993b837bd93dab18a2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96462-whttps://doaj.org/toc/2045-2322Abstract The transcriptome of SARS-CoV-2-infected cells that reflects the interplay between host and virus has provided valuable insights into mechanisms underlying SARS-CoV-2 infection and COVID-19 disease progression. In this study, we show that SARS-CoV-2 can establish a robust infection in HEK293T cells that overexpress human angiotensin-converting enzyme 2 (hACE2) without triggering significant host immune response. Instead, endoplasmic reticulum stress and unfolded protein response-related pathways are predominantly activated. By comparing our data with published transcriptome of SARS-CoV-2 infection in other cell lines, we found that the expression level of hACE2 directly correlates with the viral load in infected cells but not with the scale of immune responses. Only cells that express high level of endogenous hACE2 exhibit an extensive immune attack even with a low viral load. Therefore, the infection route may be critical for the extent of the immune response, thus the severity of COVID-19 disease status.Guihua SunQi CuiGustavo GarciaCheng WangMingzi ZhangVaithilingaraja ArumugaswamiArthur D. RiggsYanhong ShiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Guihua Sun
Qi Cui
Gustavo Garcia
Cheng Wang
Mingzi Zhang
Vaithilingaraja Arumugaswami
Arthur D. Riggs
Yanhong Shi
Comparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses
description Abstract The transcriptome of SARS-CoV-2-infected cells that reflects the interplay between host and virus has provided valuable insights into mechanisms underlying SARS-CoV-2 infection and COVID-19 disease progression. In this study, we show that SARS-CoV-2 can establish a robust infection in HEK293T cells that overexpress human angiotensin-converting enzyme 2 (hACE2) without triggering significant host immune response. Instead, endoplasmic reticulum stress and unfolded protein response-related pathways are predominantly activated. By comparing our data with published transcriptome of SARS-CoV-2 infection in other cell lines, we found that the expression level of hACE2 directly correlates with the viral load in infected cells but not with the scale of immune responses. Only cells that express high level of endogenous hACE2 exhibit an extensive immune attack even with a low viral load. Therefore, the infection route may be critical for the extent of the immune response, thus the severity of COVID-19 disease status.
format article
author Guihua Sun
Qi Cui
Gustavo Garcia
Cheng Wang
Mingzi Zhang
Vaithilingaraja Arumugaswami
Arthur D. Riggs
Yanhong Shi
author_facet Guihua Sun
Qi Cui
Gustavo Garcia
Cheng Wang
Mingzi Zhang
Vaithilingaraja Arumugaswami
Arthur D. Riggs
Yanhong Shi
author_sort Guihua Sun
title Comparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses
title_short Comparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses
title_full Comparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses
title_fullStr Comparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses
title_full_unstemmed Comparative transcriptomic analysis of SARS-CoV-2 infected cell model systems reveals differential innate immune responses
title_sort comparative transcriptomic analysis of sars-cov-2 infected cell model systems reveals differential innate immune responses
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/0f087bf8808a4cf993b837bd93dab18a
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AT qicui comparativetranscriptomicanalysisofsarscov2infectedcellmodelsystemsrevealsdifferentialinnateimmuneresponses
AT gustavogarcia comparativetranscriptomicanalysisofsarscov2infectedcellmodelsystemsrevealsdifferentialinnateimmuneresponses
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AT yanhongshi comparativetranscriptomicanalysisofsarscov2infectedcellmodelsystemsrevealsdifferentialinnateimmuneresponses
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