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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Moriyama, Masaru Kato, Naoya Otsuka, Motoyuki Shao, Run-Xuan Taniguchi, Hiroyoshi Kawabe, Takao Omata, Masao |
| Description | Country affiliation: Japan Author Affiliation: Moriyama M ( Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.) |
| Abstract | Innate immunity is part of the antiviral response. Interferon (IFN)-beta plays a leading role in this system. To investigate the influence of hepatitis C virus (HCV) on innate immunity, we examined the effect of viral proteins on IFN-beta induction. HepG2 cells were co-transfected with plasmids for seven HCV proteins (core protein, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) and the IFN-beta promoter luciferase. Toll-like receptor (TLR) 3 and Toll/IL-1 receptor domain-containing adapter inducing IFN-beta (TRIF) play key roles in dsRNA-mediated activation of interferon regulatory factor (IRF)-3 and IFN-beta; therefore, the participation of TLR3/TRIF in NS5B-mediated IFN induction was examined. Among seven HCV proteins, only NS5B, a viral RNA-dependent RNA polymerase (RdRp), activated the IFN-beta promoter. However, mutant NS5B without RdRp activity or template/primer association did not activate the IFN-beta promoter. Activation of the IFN-beta promoter by NS5B required the positive regulatory domain III, a binding sequence for IRF-3. Moreover, IRF-3 was phosphorylated by NS5B. Both inhibition of TLR3 expression by small interfering RNA and expression of the dominant negative form of TRIF significantly reduced NS5B-induced activation of IFN-beta. Of the six other HCV proteins, NS4A, NS4B, and NS5A efficiently inhibited this activation. HCV NS5B is a potent activator of the host innate immune system, possibly through TLR3/TRIF and synthesis of dsRNA. Meanwhile, NS4A, NS4B, and NS5A block IFN-beta induction by NS5B, which may contribute toward the persistence of this virus. |
| File Format | HTM / HTML |
| ISSN | 19360533 |
| e-ISSN | 19360541 |
| DOI | 10.1007/s12072-007-9003-8 |
| Journal | Hepatology International |
| Issue Number | 2 |
| Volume Number | 1 |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2007-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Gastroenterology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Hepatology |
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