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.
Biochem Biophys Res Commun. 2021 Nov 19;579:141-145. doi: 10.1016/j.bbrc.2021.09.024. Epub 2021 Sep 15.
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.
新型严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）病毒是导致目前 COVID-19 大流行的罪魁祸首，现已在全球感染超过 2 亿人，造成超过 400 万人死亡。最近的数据表明，在已康复的患者中，感染结束后，症状和全身不适可能会持续很长时间，这表明 SARS-CoV-2 感染对宿主细胞有深远的影响。在这里，我们报告 SARS-CoV-2 感染可在非洲绿猴肾细胞（Vero E6）中引发 DNA 损伤反应（DDR）。我们观察到感染细胞中 ATR 相关蛋白（ATR）的转录上调。此外，我们观察到 CHK1 的磷酸化增强，CHK1 是 ATR DNA 损伤反应的下游效应物，以及 H2AX。引人注目的是，SARS-CoV-2 感染降低了端粒结合因子 2（TRF2）庇护蛋白复合物的表达，并减少了感染的 Vero E6 细胞中的端粒长度。因此，我们的观察结果表明，SARS-CoV-2 可能会对宿主细胞产生病理后果，而不仅仅是引发免疫病理免疫反应。
