Nei-like DNA glycosylase 2 selectively antagonizes interferon-β expression upon respiratory syncytial virus infection.
Nei-like DNA glycosylase 2 selectively antagonizes interferon-β expression upon respiratory syncytial virus infection.
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DOI：
10.1016/j.jbc.2023.105028
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发表时间：
2023-08
影响因子：
4.8
通讯作者：
Boldogh, Istvan
中科院分区：
文献类型：
--
作者：
Pan, Lang;Xue, Yaoyao;Wang, Ke;Zheng, Xu;Islam, Azharul;Tapryal, Nisha;Chakraborty, Anirban;Bacsi, Attila;Ba, Xueqing;Hazra, Tapas K.;Boldogh, Istvan
作为抗病毒反应的一部分，细胞激活I型干扰素（IFN）和促炎介质的表达以控制病毒传播。病毒感染可以影响DNA完整性;然而，DNA损伤修复如何协调抗病毒反应仍然是难以捉摸的。Nei样DNA糖基化酶2（Nei-like DNA glycosylase 2，NEIL 2）是一种转录偶联的DNA修复蛋白，它能主动识别呼吸道合胞病毒（RSV）感染诱导的DNA氧化底物，从而设定IFN-β表达的阈值。我们的研究结果表明，NEIL 2拮抗核因子κB（NF-κB）在感染后早期作用于IFN-β启动子，从而限制I型IFN扩增的基因表达。缺乏Neil 2的小鼠更容易受到RSV诱导的疾病的影响，促炎基因和组织损伤的过度表达，并且将NEIL 2蛋白施用到气道中纠正了这些缺陷。这些结果表明NEIL 2在控制IFN-β水平对抗RSV感染中的保护功能。由于I型干扰素在抗病毒治疗中的短期和长期副作用，NEIL 2不仅可以确保基因组的保真度，还可以控制免疫反应。
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.
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影响因子：
21.3
作者：
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通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
4.8
作者：
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Hazra, TK
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5.4
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Szabó, C
影响因子：
6.4
作者：
Haeberle, HA;Takizawa, R;Garofalo, RP
通讯作者：
Garofalo, RP