학술논문
Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5′-UTR of TRIM22
Document Type
Academic Journal
Author
Lim, Keo-Heun; Park, Eun-Sook; Kim, Doo Hyun; Cho, Kyung Cho; Kim, Kwang Pyo; Park, Yong Kwang; Ahn, Sung Hyun; Park, Seung Hwa; Kim, Kee-Hwan; Kim, Chang Wook; Kang, Hong Seok; Lee, Ah Ram; Park, Soree; Sim, Heewoo; Won, Juhee; Seok, Kieun; You, Jueng Soo; Lee, Jeong-Hoon; Yi, Nam-Joon; Lee, Kwang-Woong; Suh, Kyung-Suk; Seong, Baik L; Kim, Kyun-Hwan
Source
Gut. Jan 01, 2018 67(1):166-178
Subject
Language
English
ISSN
0017-5749
Abstract
OBJECTIVE: Interferons (IFNs) mediate direct antiviral activity. They play a crucial role in the early host immune response against viral infections. However, IFN therapy for HBV infection is less effective than for other viral infections. DESIGN: We explored the cellular targets of HBV in response to IFNs using proteome-wide screening. RESULTS: Using LC-MS/MS, we identified proteins downregulated and upregulated by IFN treatment in HBV X protein (HBx)-stable and control cells. We found several IFN-stimulated genes downregulated by HBx, including TRIM22, which is known as an antiretroviral protein. We demonstrated that HBx suppresses the transcription of TRIM22 through a single CpG methylation in its 5′-UTR, which further reduces the IFN regulatory factor-1 binding affinity, thereby suppressing the IFN-stimulated induction of TRIM22. CONCLUSIONS: We verified our findings using a mouse model, primary human hepatocytes and human liver tissues. Our data elucidate a mechanism by which HBV evades the host innate immune system.