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SARS-CoV-2 triggers DNA damage response in Vero E6 cells

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the current COVID-19 pandemic and has now infected more than 200 million people with more than 4 million deaths globally. Recent data suggest that symptoms and general malaise may continue long after the inf...

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Autores principales: Victor, Joshua, Deutsch, Jamie, Whitaker, Annalis, Lamkin, Erica N., March, Anthony, Zhou, Pei, Botten, Jason W., Chatterjee, Nimrat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440005/
https://www.ncbi.nlm.nih.gov/pubmed/34600299
http://dx.doi.org/10.1016/j.bbrc.2021.09.024
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author Victor, Joshua
Deutsch, Jamie
Whitaker, Annalis
Lamkin, Erica N.
March, Anthony
Zhou, Pei
Botten, Jason W.
Chatterjee, Nimrat
author_facet Victor, Joshua
Deutsch, Jamie
Whitaker, Annalis
Lamkin, Erica N.
March, Anthony
Zhou, Pei
Botten, Jason W.
Chatterjee, Nimrat
author_sort Victor, Joshua
collection PubMed
description The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the current COVID-19 pandemic and has now infected more than 200 million people with more than 4 million deaths globally. Recent data suggest that symptoms and general malaise may continue long after the infection has ended in recovered patients, suggesting that SARS-CoV-2 infection has profound consequences in the host cells. Here we report that SARS-CoV-2 infection can trigger a DNA damage response (DDR) in African green monkey kidney cells (Vero E6). We observed a transcriptional upregulation of the Ataxia telangiectasia and Rad3 related protein (ATR) in infected cells. In addition, we observed enhanced phosphorylation of CHK1, a downstream effector of the ATR DNA damage response, as well as H2AX. Strikingly, SARS-CoV-2 infection lowered the expression of TRF2 shelterin-protein complex, and reduced telomere lengths in infected Vero E6 cells. Thus, our observations suggest SARS-CoV-2 may have pathological consequences to host cells beyond evoking an immunopathogenic immune response.
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spelling pubmed-84400052021-09-15 SARS-CoV-2 triggers DNA damage response in Vero E6 cells Victor, Joshua Deutsch, Jamie Whitaker, Annalis Lamkin, Erica N. March, Anthony Zhou, Pei Botten, Jason W. Chatterjee, Nimrat Biochem Biophys Res Commun Article The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the current COVID-19 pandemic and has now infected more than 200 million people with more than 4 million deaths globally. Recent data suggest that symptoms and general malaise may continue long after the infection has ended in recovered patients, suggesting that SARS-CoV-2 infection has profound consequences in the host cells. Here we report that SARS-CoV-2 infection can trigger a DNA damage response (DDR) in African green monkey kidney cells (Vero E6). We observed a transcriptional upregulation of the Ataxia telangiectasia and Rad3 related protein (ATR) in infected cells. In addition, we observed enhanced phosphorylation of CHK1, a downstream effector of the ATR DNA damage response, as well as H2AX. Strikingly, SARS-CoV-2 infection lowered the expression of TRF2 shelterin-protein complex, and reduced telomere lengths in infected Vero E6 cells. Thus, our observations suggest SARS-CoV-2 may have pathological consequences to host cells beyond evoking an immunopathogenic immune response. Elsevier Inc. 2021-11-19 2021-09-15 /pmc/articles/PMC8440005/ /pubmed/34600299 http://dx.doi.org/10.1016/j.bbrc.2021.09.024 Text en © 2021 Elsevier Inc. 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
Victor, Joshua
Deutsch, Jamie
Whitaker, Annalis
Lamkin, Erica N.
March, Anthony
Zhou, Pei
Botten, Jason W.
Chatterjee, Nimrat
SARS-CoV-2 triggers DNA damage response in Vero E6 cells
title SARS-CoV-2 triggers DNA damage response in Vero E6 cells
title_full SARS-CoV-2 triggers DNA damage response in Vero E6 cells
title_fullStr SARS-CoV-2 triggers DNA damage response in Vero E6 cells
title_full_unstemmed SARS-CoV-2 triggers DNA damage response in Vero E6 cells
title_short SARS-CoV-2 triggers DNA damage response in Vero E6 cells
title_sort sars-cov-2 triggers dna damage response in vero e6 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440005/
https://www.ncbi.nlm.nih.gov/pubmed/34600299
http://dx.doi.org/10.1016/j.bbrc.2021.09.024
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