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

SARS-CoV-2 triggers DNA damage response in Vero E6 cells.
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DOI:
10.1016/j.bbrc.2021.09.024
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发表时间:
2021-11-19
影响因子:
3.1
通讯作者:
Chatterjee N
Chatterjee N
中科院分区:
生物学4区
文献类型:
--
作者:
Victor J;Deutsch J;Whitaker A;Lamkin EN;March A;Zhou P;Botten JW;Chatterjee N

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新型严重急性呼吸道综合征冠状病毒2(SARS-CoV-2)病毒是当前COVID-19大流行的罪魁祸首,目前已感染全球2亿多人,死亡人数超过400万。最近的数据表明,症状和全身不适可能会持续很长一段时间后,感染已经结束,在康复的患者,这表明SARS-CoV-2感染有深刻的后果,在宿主细胞。在这里,我们报告说,SARS-CoV-2感染可以触发非洲绿色猴肾细胞(Vero E6)的DNA损伤反应(DDR)。我们观察到在感染细胞中共济失调毛细血管扩张和Rad 3相关蛋白(ATR)的转录上调。此外,我们观察到增强的磷酸化CHK 1,下游效应的ATR DNA损伤反应,以及H2 AX。引人注目的是,SARS-CoV-2感染降低了TRF 2 shelterin蛋白复合物的表达,并减少了感染的Vero E6细胞中的端粒长度。因此,我们的观察表明SARS-CoV-2可能对宿主细胞产生病理后果,而不仅仅是引起免疫病理性免疫应答。
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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