Hemin protects against Zika virus infection by disrupting virus-endosome fusion
文献类型:期刊论文
作者 | Xu, Meng-Meng1,3; Wu, Bing1,2; Huang, Guan-Gen1,3; Feng, Chun-Lan1; Wang, Xiao-Han1,2; Wang, Hao-Yu1,2; Wu, Yan-Wei1; Tang, Wei1,3 |
刊名 | ANTIVIRAL RESEARCH |
出版日期 | 2022-07-01 |
卷号 | 203页码:11 |
ISSN号 | 0166-3542 |
关键词 | Zika virus Hemin Antiviral Inflammation HO-1 Viral fusion |
DOI | 10.1016/j.antiviral.2022.105347 |
通讯作者 | Wu, Yan-Wei(wuyanwei@simm.ac.cn) ; Tang, Wei(tangwei@simm.ac.cn) |
英文摘要 | Zika virus (ZIKV) is a flavivirus that causes severe neuropathology in newborns and adults. There is no ZIKVspecific treatment or preventative. Therefore, it is urgent to develop safe and effective anti-ZIKV agents. Hemin, an iron-binding porphyrin, has been authorized by FDA to treat acute porphyria since the 1970s. Here, we aim to evaluate the anti-ZIKV effect of hemin in SNB-19 cells (a human glioma cell line) and explore the underlying mechanism based on the virus life cycle and functions of the host cell. Our study found that hemin has a strong activity to protect SNB-19 cells from ZIKV infection presented by decreased expression of viral proteins and virus yield. Meanwhile, ZIKV infection caused STAT1/IRF1 signaling activation and induced inflammatory responses in SNB-19 cells, which was relieved by hemin treatment. HO-1 has been reported to be potently induced by hemin and play a broad-spectrum antiviral effect. Intriguingly, hemin could still exert anti-ZIKV activity upon HO-1 siRNA treatment. Then, we conducted a time-of-addition assay, the result indicated hemin works mainly by interfering with the virus entry process. Further experiments excluded the effects of hemin on AXL-dependent viral adsorption and clathrin-mediated endocytosis processes. Subsequently, by fluorescence spectroscopy studies, intracellular fusion assay and syncytia formation assay, we revealed that hemin acts on the process of virus-endosome fusion. This study elaborated that hemin could play anti-ZIKV activity by disrupting the virus-endosome fusion process and shed new light on developing novel agents against ZIKV infection. |
WOS关键词 | HEPATITIS-B-VIRUS ; IMMUNE-RESPONSE ; OXYGENASE-1 ; INFLAMMATION ; INTERFERON ; REPLICATION ; INDUCTION |
资助项目 | National Natural Science Foundation of China, China[82173823] ; National Key R&D Program of China[2021YFC2300700] |
WOS研究方向 | Pharmacology & Pharmacy ; Virology |
语种 | 英语 |
出版者 | ELSEVIER |
WOS记录号 | WOS:000808675700004 |
源URL | [http://119.78.100.183/handle/2S10ELR8/301554] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Wu, Yan-Wei; Tang, Wei |
作者单位 | 1.Shanghai Inst Mat Med, Chinese Acad Sci, Lab Antiinflammat & Immunopharmacol, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China |
推荐引用方式 GB/T 7714 | Xu, Meng-Meng,Wu, Bing,Huang, Guan-Gen,et al. Hemin protects against Zika virus infection by disrupting virus-endosome fusion[J]. ANTIVIRAL RESEARCH,2022,203:11. |
APA | Xu, Meng-Meng.,Wu, Bing.,Huang, Guan-Gen.,Feng, Chun-Lan.,Wang, Xiao-Han.,...&Tang, Wei.(2022).Hemin protects against Zika virus infection by disrupting virus-endosome fusion.ANTIVIRAL RESEARCH,203,11. |
MLA | Xu, Meng-Meng,et al."Hemin protects against Zika virus infection by disrupting virus-endosome fusion".ANTIVIRAL RESEARCH 203(2022):11. |
入库方式: OAI收割
来源:上海药物研究所
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