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.
- HEPATITIS B
- INFECTIOUS DISEASE
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K-HL and E-SP contributed equally.
Contributors Study conception and design: K-HL, E-SP and K-HK. Acquisition of data: K-HL, E-SP, KCC, YKP, DHK, SHA, SHP, HSK, ARL, SP, HS and JW. Analysis and interpretation of data: K-HL, E-SP, KPK, JSY, BLS and KHK. Material support: K-HK, CWK, J-HL, N-JY, K-WL and K-SS. Obtained funding: K-HK and E-SP. Drafted the manuscript: K-HL, E-SP and K-HK.
Funding This study was supported by the National Research Foundation (NRF) grant funded by the Korean government (No. 2013R1A2A2A01068194, No. 2014M3A9A8064633, NRF-2016R1A5A2012284 and 2016R1A2B4007531). This research was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute , funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI14C-1529-020014).
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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