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 Das (), Pradipta Ghosh (), Istvan Boldogh () and Tapas K. Hazra ()
Additional contact information
Nisha Tapryal: University of Texas Medical Branch
Anirban Chakraborty: University of Texas Medical Branch
Kaushik Saha: University of California, San Diego
Azharul Islam: University of Texas Medical Branch
Lang Pan: University of Texas Medical Branch
Koa Hosoki: Immunology Allergy and Rheumatology, Baylor College of Medicine
Ibrahim M. Sayed: University of California
Jason M. Duran: UC San Diego Medical Center
Joshua Alcantara: University of California San Diego
Vanessa Castillo: University of California San Diego
Courtney Tindle: University of California San Diego
Altaf H. Sarker: Life Sciences Division, Lawrence Berkeley National Laboratory
Maki Wakamiya: University of Texas Medical Branch
Victor J. Cardenas: University of Texas Medical Branch
Gulshan Sharma: University of Texas Medical Branch
Laura E. Crotty Alexander: University of California
Sanjiv Sur: Immunology Allergy and Rheumatology, Baylor College of Medicine
Debashis Sahoo: University of California San Diego
Gourisankar Ghosh: University of California, San Diego
Soumita Das: University of California
Pradipta Ghosh: University of California San Diego
Istvan Boldogh: University of Texas Medical Branch
Tapas K. Hazra: University of Texas Medical Branch

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43938-0

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