Yang Qingran, Guo Haoran, Li Huili, Li Zhaoxue, Ni Fushun, Wen Zhongmei, Liu Kai, Kong Huihui, Wei Wei
Department of Respiration, Children's Medical Center, First Hospital, Jilin University, Changchun, Jilin, China.
Institute of Virology and AIDS Research, First Hospital, Jilin University, Changchun, Jilin, China.
Nat Commun. 2025 Feb 17;16(1):1715. doi: 10.1038/s41467-025-57094-0.
Respiratory viruses pose an ongoing threat to human health with excessive cytokine secretion contributing to severe illness and mortality. However, the relationship between cytokine secretion and viral infection remains poorly understood. Here we elucidate the role of CXCL8 as an early response gene to EV-D68 infection. Silencing CXCL8 or its receptors, CXCR1/2, impedes EV-D68 replication in vitro. Upon recognition of CXCL8 by CXCR1/2, the MAPK pathway is activated, facilitating the translocation of nuclear hnRNP-K to the cytoplasm. This translocation increases the recognition of viral RNA by hnRNP-K in the cytoplasm, promoting the function of the 5' untranslated region in the viral genome. Moreover, our investigations also reveal the importance of the CXCL8 signaling pathway in the replication of both influenza virus and rhinovirus. In summary, our findings hint that these viruses exploit the CXCL8/MAPK/hnRNP-K axis to enhance viral replication in respiratory cells in vitro.
呼吸道病毒持续威胁着人类健康，过量的细胞因子分泌会导致严重疾病和死亡。然而，细胞因子分泌与病毒感染之间的关系仍知之甚少。在此，我们阐明了CXCL8作为肠道病毒D68（EV-D68）感染早期反应基因的作用。沉默CXCL8或其受体CXCR1/2会阻碍EV-D68在体外的复制。当CXCR1/2识别CXCL8后，丝裂原活化蛋白激酶（MAPK）途径被激活，促进核不均一核糖核蛋白K（hnRNP-K）向细胞质的转运。这种转运增加了hnRNP-K在细胞质中对病毒RNA的识别，促进了病毒基因组5'非翻译区的功能。此外，我们的研究还揭示了CXCL8信号通路在流感病毒和鼻病毒复制中的重要性。总之，我们的研究结果表明，这些病毒利用CXCL8/MAPK/hnRNP-K轴在体外增强呼吸道细胞中的病毒复制。
