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 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. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Lang Pan, Yaoyao Xue, Ke Wang, Xu Zheng, Azharul Islam, Nisha Tapryal, Anirban Chakraborty, Attila Bacsi, Xueqing Ba, Tapas K Hazra, Istvan Boldogh. Nei-like DNA glycosylase 2 selectively antagonizes interferon-β expression upon respiratory syncytial virus infection. The Journal of biological chemistry. 2023 Aug;299(8):105028

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PMID: 37423306

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