Nei-like DNA glycosylase 2 selectively antagonizes interferon-β expression upon respiratory syncytial virus infection

Lang Pan, Yaoyao Xue, Ke Wang, Xu Zheng, Azharul Islam, Nisha Tapryal, Anirban Chakraborty, Attila Bacsi, Xueqing Ba, Tapas K. Hazra, Istvan Boldogh

Research output: Contribution to journalArticlepeer-review

Abstract

As part of the antiviral response, cells activate the expressions of type I interferons (IFNs) and proinflammatory mediators to control viral spreading. Viral infections can impact DNA integrity; however, how DNA damage repair coordinates antiviral response remains elusive. Here we report Nei-like DNA glycosylase 2 (NEIL2), a transcription-coupled DNA repair protein, actively recognizes the oxidative DNA substrates induced by respiratory syncytial virus (RSV) infection to set the threshold of IFN-β expression. Our results show that NEIL2 antagonizes nuclear factor κB (NF-κB) acting on the IFN-β promoter early after infection, thus limiting gene expression amplified by type I IFNs. Mice lacking Neil2 are far more susceptible to RSV-induced illness with an exuberant expression of proinflammatory genes and tissue damage, and the administration of NEIL2 protein into the airway corrected these defects. These results suggest a safeguarding function of NEIL2 in controlling IFN-β levels against RSV infection. Due to the short- and long-term side effects of type I IFNs applied in antiviral therapy, NEIL2 may provide an alternative not only for ensuring genome fidelity but also for controlling immune responses.

Original languageEnglish (US)
Article number105028
JournalJournal of Biological Chemistry
Volume299
Issue number8
DOIs
StatePublished - Aug 2023

Keywords

  • DNA damage
  • NF-κB
  • antiviral response
  • inflammation
  • innate immunity
  • oxidative stress
  • transcription regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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