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

Joshua Victor; Jamie Deutsch; Annalis Whitaker; Erica N Lamkin; Anthony March; Pei Zhou; Jason W Botten; Nimrat Chatterjee

doi:10.1016/j.bbrc.2021.09.024

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

Biochem Biophys Res Commun. 2021 Nov 19:579:141-145. doi: 10.1016/j.bbrc.2021.09.024. Epub 2021 Sep 15.

Authors

Joshua Victor¹, Jamie Deutsch¹, Annalis Whitaker², Erica N Lamkin¹, Anthony March¹, Pei Zhou³, Jason W Botten⁴, Nimrat Chatterjee⁵

Affiliations

¹ Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA.
² Division of Immunobiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA.
³ Department of Biochemistry, Duke University School of Medicine, Durham, NC, 27710, USA.
⁴ Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA; Division of Immunobiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA.
⁵ Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA; Division of Immunobiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA; University of Vermont Cancer Center, University of Vermont, Burlington, VT, 05405, USA. Electronic address: nimrat.chatterjee@med.uvm.edu.

Abstract

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.

Keywords: DNA damage Response; Genome instability; SARS-CoV-2; Telomeres.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Ataxia Telangiectasia Mutated Proteins / genetics
COVID-19 / genetics*
Checkpoint Kinase 1 / metabolism
Chlorocebus aethiops
DNA Damage*
Histones / genetics
Host-Pathogen Interactions / genetics*
Phosphorylation
SARS-CoV-2 / pathogenicity*
Telomere
Vero Cells

Substances

Histones
Ataxia Telangiectasia Mutated Proteins
Checkpoint Kinase 1

Grants and funding

T32 AI055402/AI/NIAID NIH HHS/United States