Hepatitis C Virus Induces the Ubiquitin-Editing Enzyme A20 via Depletion of the Transcription Factor Upstream Stimulatory Factor 1 To Support Its Replication

Autor: Ja Yeon Kim, Stephanie T. Chan, Jing-hsiung James Ou, Jiyoung Lee
Rok vydání: 2019
Předmět:
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
Zdroj: mBio, Vol 10, Iss 4, p e01660-19 (2019)
mBio
mBio, Vol 10, Iss 4 (2019)
ISSN: 2150-7511
2161-2129
DOI: 10.1128/mbio.01660-19
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: