IL-1 beta Enhances the Antiviral Effect of IFN-alpha on HCV Replication by Negatively Modulating ERK2 Activation

doi:10.1021/acsinfecdis.9b00506

	IL-1 beta Enhances the Antiviral Effect of IFN-alpha on HCV Replication by Negatively Modulating ERK2 Activation
	Guo, Mingzhe1,2,3 ; Ye, Liqing1,2,3 ; Yu, Tao 1; Han, Lin1,2,3 ; Li, Qingchao 1; Lou, Peilan1,2,3 ; Gan, Tianyu 1,3; Jin, Xia 1,2,3; Xiao, Hui 1,3; Meng, Guangxun 1,3; Zhong, Jin1,2,3 ; Xu, Yongfen 1
	2020-07-10
发表期刊	ACS INFECTIOUS DISEASES (IF:4.0[JCR-2023],4.3[5-Year])
ISSN	2373-8227
卷号	6 期号:7 页码:1708-1718
DOI	10.1021/acsinfecdis.9b00506
摘要	Chronic hepatitis C infection is a leading cause of liver cirrhosis, which is linked to chronic hepatic inflammation. While there are multiple studies detailing the proinflammatory role of interleukin-1 beta (IL-1 beta) in HCV-induced inflammasome signaling, the antiviral capacity of this cytokine has not been adequately investigated in the context of HCV infection or other members of Flaviridae. Our data indicated that IL-beta alone does not inhibit HCV replication, yet when in combination with IFN-alpha, it can boost the anti-HCV activity of IFN-alpha, which is mediated by augmented STATI tyrosine 701 phosphorylation. Through signaling inhibitor screening, we found that ERK2 kinase is directly linked to the enhanced activation of the STAT 1 complex. Our study found that IL-1 beta negatively affects ERK2 phosphorylation, which suggests that IL-1 beta-mediated STAT1 tyrosine 701 phosphorylation employed kinase machinery of ERK2 other than JNK or P38 kinase. Our results identify IL-1 beta as a proinflammatory cytokine possessing wide spectrum synergistic antiviral capability via enhancing IFN-alpha-induced interferon-stimulated genes (ISGs) expression. A more nuanced understanding of the antiviral mechanisms of this important cytokine could facilitate the development of new therapeutic options.
关键词	HCV ISG STATI ERK2 IL-1 beta IFN-alpha
收录类别	SCIE
语种	英语
WOS研究方向	Pharmacology & Pharmacy ; Infectious Diseases
WOS类目	Chemistry, Medicinal ; Infectious Diseases
WOS记录号	WOS:000595290900022
出版者	AMER CHEMICAL SOC
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/243237
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_钟劲组生命科学与技术学院_硕士生
通讯作者	Zhong, Jin; Xu, Yongfen
作者单位	1.Chinese Acad Sci, Inst Pasteur Shanghai, CAS Key Lab Mol Virol & Immunol, Shanghai, Peoples R China; 2.ShanghaiTech Univ, Shanghai 201210, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
第一作者单位	上海科技大学
通讯作者单位	上海科技大学
推荐引用方式 GB/T 7714	Guo, Mingzhe,Ye, Liqing,Yu, Tao,et al. IL-1 beta Enhances the Antiviral Effect of IFN-alpha on HCV Replication by Negatively Modulating ERK2 Activation[J]. ACS INFECTIOUS DISEASES,2020,6(7):1708-1718.
APA	Guo, Mingzhe.,Ye, Liqing.,Yu, Tao.,Han, Lin.,Li, Qingchao.,...&Xu, Yongfen.(2020).IL-1 beta Enhances the Antiviral Effect of IFN-alpha on HCV Replication by Negatively Modulating ERK2 Activation.ACS INFECTIOUS DISEASES,6(7),1708-1718.
MLA	Guo, Mingzhe,et al."IL-1 beta Enhances the Antiviral Effect of IFN-alpha on HCV Replication by Negatively Modulating ERK2 Activation".ACS INFECTIOUS DISEASES 6.7(2020):1708-1718.