Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5'-UTR of TRIM22

Keo Heun Lim, Eun Sook Park, Doo Hyun Kim, Kyung Cho Cho, Kwang Pyo Kim, Yong Kwang Park, Sung Hyun Ahn, Seung Hwa Park, Kee Hwan Kim, Chang Wook Kim, Hong Seok Kang, Ah Ram Lee, Soree Park, Heewoo Sim, Juhee Won, Kieun Seok, Jueng Soo You, Jeong Hoon Lee, Nam Joon Yi, Kwang Woong LeeKyung Suk Suh, Baik L. Seong, Kyun Hwan Kim

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17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)166-178
Number of pages13
JournalGut
Volume67
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Lim, K. H., Park, E. S., Kim, D. H., Cho, K. C., Kim, K. P., Park, Y. K., Ahn, S. H., Park, S. H., Kim, K. H., Kim, C. W., Kang, H. S., Lee, A. R., Park, S., Sim, H., Won, J., Seok, K., You, J. S., Lee, J. H., Yi, N. J., ... Kim, K. H. (2018). Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5'-UTR of TRIM22. Gut, 67(1), 166-178. https://doi.org/10.1136/gutjnl-2016-312742