Severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) has led to the coronavirus disease 2019 (COVID–19) pandemic, severely affecting public health and the global economy. Adaptive immunity plays a crucial role in fighting against SARS–CoV–2 infection and directly influences the clinical outcomes of patients. Clinical studies have indicated that patients with severe COVID–19 exhibit delayed and weak adaptive immune responses; however, the mechanism by which SARS–CoV–2 impedes adaptive immunity remains unclear. Here, by using an in vitro cell line, we report that the SARS–CoV–2 spike protein significantly inhibits DNA damage repair, which is required for effective V(D)J recombination in adaptive immunity. Mechanistically, we found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site. Our findings reveal a potential molecular mechanism by which the spike protein might impede adaptive immunity and underscore the potential side effects of full-length spike-based vaccines.

中文翻译：

---

SARS–CoV–2 刺突会损害 DNA 损伤修复并抑制体外 V(D)J 重组


严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 导致了 2019 年冠状病毒病 (COVID-19) 大流行，严重影响了公共卫生和全球经济。适应性免疫在对抗 SARS-CoV-2 感染中发挥着至关重要的作用，并直接影响患者的临床结果。临床研究表明，重症COVID-19患者表现出延迟且较弱的适应性免疫反应；然而，SARS-CoV-2 阻碍适应性免疫的机制仍不清楚。在这里，通过使用体外细胞系，我们报告 SARS-CoV-2 刺突蛋白显着抑制 DNA 损伤修复，这是适应性免疫中有效 V(D)J 重组所必需的。从机制上讲，我们发现刺突蛋白定位于细胞核，并通过阻止关键 DNA 修复蛋白 BRCA1 和 53BP1 募集到损伤位点来抑制 DNA 损伤修复。我们的研究结果揭示了刺突蛋白可能阻碍适应性免疫的潜在分子机制，并强调了全长刺突疫苗的潜在副作用。