Hepatitis C Virus Induces the Ubiquitin-Editing Enzyme A20 via Depletion of the Transcription Factor Upstream Stimulatory Factor 1 To Support Its Replication
| العنوان: | Hepatitis C Virus Induces the Ubiquitin-Editing Enzyme A20 via Depletion of the Transcription Factor Upstream Stimulatory Factor 1 To Support Its Replication |
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| المؤلفون: | Ja Yeon Kim, Stephanie T. Chan, Jing-hsiung James Ou, Jiyoung Lee |
| المصدر: | mBio, Vol 10, Iss 4, p e01660-19 (2019) mBio mBio, Vol 10, Iss 4 (2019) |
| بيانات النشر: | American Society for Microbiology, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | hcv ires, Hepacivirus, Virus Replication, Microbiology, Upstream Stimulatory Factor, Host-Microbe Biology, Cell Line, 03 medical and health sciences, immune system diseases, hemic and lymphatic diseases, Virology, medicine, Humans, a20 ubiquitin enzyme, Gene silencing, Promoter Regions, Genetic, Transcription factor, Tumor Necrosis Factor alpha-Induced Protein 3, 030304 developmental biology, 0303 health sciences, Host Microbial Interactions, 030306 microbiology, Chemistry, Ubiquitination, virus diseases, usf-1 transcription factor, hepatitis c virus, Hepatitis C, QR1-502, digestive system diseases, 3. Good health, Cell biology, Internal ribosome entry site, Gene Expression Regulation, Proteasome, Proteasome inhibitor, Upstream Stimulatory Factors, Signal transduction, Chromatin immunoprecipitation, Research Article, Signal Transduction, medicine.drug |
| الوصف: | Hepatitis C virus establishes chronic infection in approximately 85% of the patients whom it infects. However, the mechanism of how HCV evades host immunity to establish persistence is unclear. In this report, we demonstrate that HCV could induce the expression of the ubiquitin-editing enzyme A20, an important negative regulator of the tumor necrosis factor alpha (TNF-α) and NF-κB signaling pathways. This induction of A20 enhanced HCV replication as it could stimulate the HCV IRES activity to enhance the translation of HCV proteins. The induction of A20 was mediated by the depletion of USF-1, a suppressor of the A20 promoter. Our study thus provides important information for further understanding the interaction between HCV and its host cells. Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20, is a ubiquitin-editing enzyme capable of ubiquitination or deubiquitination of its target proteins. In this study, we show that hepatitis C virus (HCV) infection could induce the expression of A20 via the activation of the A20 promoter. The induction of A20 by HCV coincided with the loss of upstream stimulatory factor 1 (USF-1), a transcription factor known to suppress the A20 promoter. The role of USF-1 in the regulation of the A20 promoter in HCV-infected cells was confirmed by the chromatin immunoprecipitation (ChIP) assay, and its depletion was apparently mediated by proteasomes, as USF-1 could be stabilized by the proteasome inhibitor MG132 to suppress the A20 expression. As the overexpression of A20 enhanced the replication of HCV and the silencing of A20 had the opposite effect, A20 is a positive regulator of HCV replication. Our further studies indicated that A20 enhanced the activity of the HCV internal ribosome entry site (IRES). In conclusion, our results demonstrated that HCV could induce the expression of A20 via the depletion of USF-1 to enhance its replication. Our study provided important information for further understanding the interaction between HCV and its host cells. |
| تدمد: | 2150-7511 2161-2129 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7dd26c2c6b1eae2824c4bb51e85a9644Test https://doi.org/10.1128/mbio.01660-19Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7dd26c2c6b1eae2824c4bb51e85a9644 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21507511 21612129 |
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