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Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5′-UTR of TRIM22
  1. Keo-Heun Lim1,
  2. Eun-Sook Park1,
  3. Doo Hyun Kim1,
  4. Kyung Cho Cho2,
  5. Kwang Pyo Kim2,
  6. Yong Kwang Park1,
  7. Sung Hyun Ahn1,
  8. Seung Hwa Park3,
  9. Kee-Hwan Kim4,
  10. Chang Wook Kim5,
  11. Hong Seok Kang1,
  12. Ah Ram Lee1,
  13. Soree Park1,
  14. Heewoo Sim1,
  15. Juhee Won1,
  16. Kieun Seok1,
  17. Jueng Soo You6,
  18. Jeong-Hoon Lee7,
  19. Nam-Joon Yi8,
  20. Kwang-Woong Lee8,
  21. Kyung-Suk Suh8,
  22. Baik L Seong9,
  23. Kyun-Hwan Kim1,10,11
  1. 1Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea
  2. 2Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi, Korea
  3. 3Department of Anatomy, School of Medicine, Konkuk University, Seoul, Korea
  4. 4Department of Surgery, Uijeongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
  5. 5Department of Internal Medicine, Uijeongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
  6. 6Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Korea
  7. 7Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
  8. 8Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
  9. 9Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
  10. 10KU Open Innovation Center, Konkuk University, Seoul, Korea
  11. 11Research Institute of Medical Sciences, Konkuk University, Seoul, Korea
  1. Correspondence to Professor Kyun-Hwan Kim, Department of Pharmacology, School of Medicine, Konkuk University, Seoul 05029, Korea; khkim10{at}


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.


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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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