Detail Convergent transcription of interferon-stimulated genes by TNF-a and IFN-a augments antiviral activity against HCV and HEV (scientific reports, 2016, 6 (25482), 1-14) Bibliografi Author: Wang, Wenshi ; Xu, Lei ; Brandsma, Johannes H. ; Wang, Yijin ; Hakim, Mohamad S. ; Zhou, Xinying ; Yin, Yuebang ; Fuhler, Gwenny M. ; van der Laan, Luc J. W. ; van der Woude, C. Janneke ; Sprengers, Dave ; Metselaar, Herold J. ; Smits, Ron ; Poot, Raymond A. ; Peppelenbosch, Maikel P. ; Pan, Qiuwei Topik: HCV; HEV; Hepatitis - Drug Bahasa: (EN )     Tahun Terbit: 2016     Jenis: Article - diterbitkan di jurnal ilmiah internasional Fulltext: srep25482.pdf (2.52MB; 0 download) Abstract IFN-a has been used for decades to treat chronic hepatitis B and C, and as an off-label treatment for some cases of hepatitis E virus (HEV) infection. TNF-a is another important cytokine involved in inflammatory disease, which can interact with interferon signaling. Because interferon-stimulated genes (ISGs) are the ultimate antiviral effectors of the interferon signaling, this study aimed to understand the regulation of ISG transcription and the antiviral activity by IFN-a and TNF-a. In this study, treatment of TNF-a inhibited replication of HCV by 71 ± 2.4% and HEV by 41 ± 4.9%. Interestingly, TNF-a induced the expression of a panel of antiviral ISGs (2-11 fold). Blocking the TNF-a signaling by Humira abrogated ISG induction and its antiviral activity. Chip-seq data analysis and mutagenesis assay further revealed that the NF-?B protein complex, a key downstream element of TNF-a signaling, directly binds to the ISRE motif in the ISG promoters and thereby drives their transcription. This process is independent of interferons and JAK-STAT cascade. Importantly, when combined with IFN-a, TNF-a works cooperatively on ISG induction, explaining their additive antiviral effects. Thus, our study reveals a novel mechanism of convergent transcription of ISGs by TNF-a and IFN-a, which augments their antiviral activity against HCV and HEV. [hepatitis - drug] Opini Anda Klik untuk menuliskan opini Anda tentang koleksi ini! Lihat Sejarah Pengadaan  Konversi Metadata   Kembali

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