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

Author

Listed:
  • Nisha Tapryal

    (University of Texas Medical Branch)

  • Anirban Chakraborty

    (University of Texas Medical Branch)

  • Kaushik Saha

    (University of California, San Diego
    SRM University-AP)

  • 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
    University of Massachusetts-Lowell)

  • 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
    University of California San Diego)

  • Gourisankar Ghosh

    (University of California, San Diego)

  • Soumita Das

    (University of California
    University of Massachusetts-Lowell)

  • Pradipta Ghosh

    (University of California San Diego
    University of California)

  • Istvan Boldogh

    (University of Texas Medical Branch)

  • Tapas K. Hazra

    (University of Texas Medical Branch)

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.

Suggested Citation

  • 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, 2023. "The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43938-0
    DOI: 10.1038/s41467-023-43938-0
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    References listed on IDEAS

    as
    1. Anirban Chakraborty & Nisha Tapryal & Tatiana Venkova & Nobuo Horikoshi & Raj K. Pandita & Altaf H. Sarker & Partha S. Sarkar & Tej K. Pandita & Tapas K. Hazra, 2016. "Classical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    2. Changchang Cao & Zhaokui Cai & Xia Xiao & Jian Rao & Juan Chen & Naijing Hu & Minnan Yang & Xiaorui Xing & Yongle Wang & Manman Li & Bing Zhou & Xiangxi Wang & Jianwei Wang & Yuanchao Xue, 2021. "The architecture of the SARS-CoV-2 RNA genome inside virion," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Sheila S. David & Valerie L. O'Shea & Sucharita Kundu, 2007. "Base-excision repair of oxidative DNA damage," Nature, Nature, vol. 447(7147), pages 941-950, June.
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