The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection

Nisha Tapryal, Anirban Chakraborty, Kaushik Saha, Azharul Islam, Lang Pan, Koa Hosoki, Ibrahim M. Sayed, Jason M. Duran, Joshua Alcantara, Vanessa Castillo, Courtney Tindle, Altaf H. Sarker, Maki Wakamiya, Victor J Cardenas, Gulshan Sharma, Laura E. Crotty Alexander, Sanjiv Sur, Debashis Sahoo, Gourisankar Ghosh, Soumita DasPradipta Ghosh, Istvan Boldogh, Tapas K. Hazra

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number8169
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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