Interleukin-1β promotes human metapneumovirus replication via activating the cGAS-STING pathway

作者全名：Wu, Guojin; Zhang, Yueyan; Niu, Linlin; Hu, Yuan; Yang, Yuting; Zhao, Yao

作者地址：[Wu, Guojin; Zhang, Yueyan; Niu, Linlin; Yang, Yuting; Zhao, Yao] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Chongqin, Chongqing 400014, Peoples R China; [Hu, Yuan] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing, Peoples R China

通信作者：Yang, YT; Zhao, Y (通讯作者)，Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Chongqin, Chongqing 400014, Peoples R China.

来源：VIRUS RESEARCH

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001218682700001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：343

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Human metapneumovirus; IL-1 beta; cGAS-STING signaling pathway

摘要：Background: Human metapneumovirus(hMPV) is one of the most common viruses that cause acute lower respiratory tract infections. Interleukin-1 beta (IL-1 beta) has been reported to play an important role in multiple virus replication. Patients with hMPV infection have increased levels of IL-1 beta which reminds IL-1 beta is associated with hMPV infection. However, the mechanism by which IL-1 beta affects hMPV replication remains unclear. In this study, we explore the effect of IL-1 beta 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-1 beta, cyclic GMP-AMP synthase (cGAS), and interferon stimulating factor (STING). Regulating IL-1 beta 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-1 beta 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-1 beta could contribute to the decreased viral loads of hMPV. While the exogenous supplement of recombinant human IL-1 beta in cells, replication of hMPV was significantly increased. Additionally, the level of cGAS-STING protein expression would be affected by regulating IL-1 beta expression. Inhibitors of the cGAS-STING pathway led to a lower level of hMPV replication. Conclusion: This study found that IL-1 beta 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-1 beta may be an effective new strategy to restrain virus replication.

基金机构：National Clinical Research Center for Child Health and Disorders General Project and and Youth Project [NCRCCHD-2019- GP-04, NCRCCHD-2021-YP-03]; Chongqing Talent Program [CQYC20210303393]; Program for Youth Innovation in Future Medicine, Chongqing Medical University

基金资助正文：This study was supported by the National Clinical Research Center for Child Health and Disorders General Project (No. NCRCCHD-2019- GP-04) and Youth Project (No. NCRCCHD-2021-YP-03) ; Chongqing Talent Program (CQYC20210303393) ; Program for Youth Innovation in Future Medicine, Chongqing Medical University.