SARS-CoV-2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro

Viruses. 2021 Oct 13;13(10):2056. doi: 10.3390/v13102056.

Abstract

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.

Keywords: DNA damage repair; SARS–CoV–2; V(D)J recombination; spike; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adaptive Immunity / immunology*
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • BRCA1 Protein / antagonists & inhibitors
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / pathology*
  • COVID-19 Vaccines / immunology
  • Cell Line
  • DNA Damage / genetics
  • DNA Repair / genetics*
  • HEK293 Cells
  • Humans
  • Immunity, Humoral / immunology
  • Immunosuppression Therapy
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes, Helper-Inducer / immunology
  • Tumor Suppressor p53-Binding Protein 1 / antagonists & inhibitors
  • V(D)J Recombination / genetics*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • BRCA1 Protein
  • BRCA1 protein, human
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1
  • spike protein, SARS-CoV-2