Publication Date
12-9-2023
Journal
Nature Communications
DOI
10.1038/s41467-023-43938-0
PMID
38071370
PMCID
PMC10710473
PubMedCentral® Posted Date
12-9-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Cricetinae, Animals, Humans, COVID-19, DNA Glycosylases, Angiotensin-Converting Enzyme 2, SARS-CoV-2, Genome, DNA-(Apurinic or Apyrimidinic Site) Lyase, Virus-host interactions, SARS-CoV-2, Viral infection
Abstract
SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5'-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.
Included in
Allergy and Immunology Commons, Clinical Epidemiology Commons, COVID-19 Commons, Immune System Diseases Commons, Medical Genetics Commons, Medical Immunology Commons
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