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Suppression of Interferon-mediated Anti-HBV Response by a Single CpG Methylation in 5``UTR of TRIM22
( Eun-sook Park ),( Doo Hyun Kim ),( Ah Ram Lee ),( Soree Park ),( Heewoo Sim ),( Juhee Won ),( Kyun-hwan Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Background & Aims: Interferons (IFNs) mediate direct antiviral activity. It plays a crucial role in early host immune response against viral infections. However, IFN therapy for hepatitis B virus (HBV) infection is known to be less effective than in other viral infections. Methods: We explored the cellular targets of HBV in response to IFNs using proteome-wide screening. Results: We identified the down- or up-regulated proteins in model cells after the IFN treatment using LC-MS/MS. We found the several downregulated IFN-stimulated genes (ISGs) including TRIM22 known as an antiviral protein against retroviruses. We demonstrated that HBx suppresses the transcription of TRIM22 through a single CpG methylation at its 5``UTR, which further reduces the IRF1 binding affinity thereby suppressing the IFNs-stimulated induction of TRIM22. Conclusion: Our findings were verified using a mouse model and primary human hepatocytes (PHHs) and may provide a mechanism how HBV evade host innate immune system.