期刊
FASEB JOURNAL
卷 30, 期 10, 页码 3352-3367出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201600356R
关键词
innate immunity; ribavirin; transcription
资金
- European Association for the Study of the Liver (EASL), Sheila Sherlock Fellowship
- Netherlands Organization for Scientific Research (NWO/ZonMw) Veni Grant [916-13-032]
- Dutch Digestive Foundation (MLDS) Career Development Grant (CDG) [1304]
- Daniel den Hoed Foundation Centennial Award Fellowship, an Erasmus MC Medical Research Advisory Committee (MRace) grant
- China Scholarship Council [201306300027, 201206150075, 201303250056, 201207720007, 201307720045]
IFN regulatory factor 1 (IRF1) is one of the most important IFN-stimulated genes (ISGs) in cellular antiviral immunity. Although hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide, how ISGs counteract HEV infection is largely unknown. This study was conducted to investigate the effect of IRF1 on HEV replication. Multiple cell lines were used in 2 models that harbor HEV. In different HEV cell culture systems, IRF1 effectively inhibited HEV replication. IRF1 did not trigger IFN production, and chromatin immunoprecipitation sequencing data analysis revealed that IRF1 bound to the promoter region of signal transducers and activators of transcription 1 (STAT1). Functional assay confirmed that IRF1 could drive the transcription of STAT1, resulting in elevation of total and phosphorylated STAT1 proteins and further activating the transcription of a panel of downstream antiviral ISGs. By pharmacological inhibitors and RNAi-mediated gene-silencing approaches, we revealed that antiviral function of IRF1 is dependent on the JAK-STAT cascade. Furthermore, induction of ISGs and the anti-HEV effect of IRF1 overlapped that of IFN, but was potentiated by ribavirin. We demonstrated that IRF1 effectively inhibits HEV replication through the activation of the JAK-STAT pathway, and the subsequent transcription of antiviral ISGs, but independent of IFN production.-Xu, L., Zhou, X., Wang, W., Wang, Y., Yin, Y., van der Laan, L. J. W., Sprengers, D., Metselaar, H. J., Peppelenbosch, M. P., Pan, Q. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据