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

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 D...

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Bibliographic Details
Published in:The Journal of biological chemistry 2023-08, Vol.299 (8), p.105028, Article 105028
Main Authors: Pan, Lang, Xue, Yaoyao, Wang, Ke, Zheng, Xu, Islam, Azharul, Tapryal, Nisha, Chakraborty, Anirban, Bacsi, Attila, Ba, Xueqing, Hazra, Tapas K., Boldogh, Istvan
Format: Article
Language:English
Subjects:
Animals
antiviral response
DNA
DNA damage
DNA Glycosylases - genetics
inflammation
innate immunity
Interferon Type I - genetics
Interferon Type I - metabolism
Interferon-beta - genetics
Mice
NF-κB
oxidative stress
Respiratory Syncytial Virus Infections - genetics
Respiratory Syncytial Viruses - genetics
Respiratory Syncytial Viruses - immunology
transcription regulation
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Summary: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.
ISSN:0021-9258
1083-351X
1083-351X
DOI:10.1016/j.jbc.2023.105028