National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, China.
Virus Res. 2024 May;343:199344. doi: 10.1016/j.virusres.2024.199344. Epub 2024 Mar 4.
BACKGROUND: Human metapneumovirus(hMPV) is one of the most common viruses that cause acute lower respiratory tract infections. Interleukin-1β (IL-1β) has been reported to play an important role in multiple virus replication. Patients with hMPV infection have increased levels of IL-1β which reminds IL-1β is associated with hMPV infection. However, the mechanism by which IL-1β affects hMPV replication remains unclear. In this study, we explore the effect of IL-1β on hMPV replication and investigate its specific mechanism of action. METHODS: We established an hMPV infection model through Human bronchial epithelial cells (16HBE). qRT-PCR and Western Blot were used to detect the expression levels of IL-1β, cyclic GMP-AMP synthase (cGAS), and interferon stimulating factor (STING). Regulating IL-1β expression by small interfering RNA (siRNA) or exogenous supplementary to study the influence of hMPV replication. The selective cGAS inhibitor RU.521, G150, and STING inhibitor H-151 were utilized to detect hMPV replication in 16HBE cells. RESULTS: The level of IL-1β protein increased in a time-dependent and dose-dependent manner after hMPV infection. The mRNA and protein levels of cGAS and STING were significantly up-regulated. Knockdown of IL-1β could contribute to the decreased viral loads of hMPV. While the exogenous supplement of recombinant human IL-1β in cells, replication of hMPV was significantly increased. Additionally, the level of cGAS-STING protein expression would be affected by regulating IL-1β expression. Inhibitors of the cGAS-STING pathway led to a lower level of hMPV replication. CONCLUSION: This study found that IL-1β could promote hMPV replication through the cGAS-STING pathway, which has the potential to serve as a candidate to fight against hMPV infection, targeting IL-1β may be an effective new strategy to restrain virus replication.
背景：人偏肺病毒（hMPV）是引起急性下呼吸道感染的最常见病毒之一。白细胞介素-1β（IL-1β）已被报道在多种病毒复制中发挥重要作用。hMPV 感染患者的 IL-1β水平升高，这表明 IL-1β与 hMPV 感染有关。然而，IL-1β影响 hMPV 复制的确切机制尚不清楚。在这项研究中，我们探讨了 IL-1β对 hMPV 复制的影响，并研究了其具体的作用机制。
方法：我们通过人支气管上皮细胞（16HBE）建立了 hMPV 感染模型。qRT-PCR 和 Western blot 用于检测 IL-1β、环鸟苷酸-腺苷酸合酶（cGAS）和干扰素刺激因子（STING）的表达水平。通过小干扰 RNA（siRNA）或外源性补充来调节 IL-1β的表达，研究其对 hMPV 复制的影响。利用选择性 cGAS 抑制剂 RU.521、G150 和 STING 抑制剂 H-151 检测 16HBE 细胞中的 hMPV 复制。
结果：hMPV 感染后，IL-1β 蛋白水平呈时间和剂量依赖性增加。cGAS 和 STING 的 mRNA 和蛋白水平均显著上调。IL-1β 的敲低可导致 hMPV 的病毒载量降低。而细胞中重组人 IL-1β 的外源性补充则显著增加了 hMPV 的复制。此外，通过调节 IL-1β 的表达水平，cGAS-STING 蛋白表达水平也会受到影响。cGAS-STING 通路抑制剂导致 hMPV 复制水平降低。
结论：本研究发现，IL-1β 可通过 cGAS-STING 通路促进 hMPV 复制，该通路可能成为对抗 hMPV 感染的候选靶点，靶向 IL-1β 可能是一种抑制病毒复制的有效新策略。
Front Cell Infect Microbiol. 2025-7-8
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