Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5'-UTR ofTRIM22.
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.



We explored the cellular targets of HBV in response to IFNs using proteome-wide screening.



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, includingTRIM22, which is known as an antiretroviral protein. We demonstrated that HBx suppresses the transcription ofTRIM22through a single CpG methylation in its 5'-UTR, which further reduces the IFN regulatory factor-1 binding affinity, thereby suppressing the IFN-stimulated induction ofTRIM22.



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.
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Keo-Heun
KH
Lim
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Eun-Sook
ES
Park
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Doo Hyun
DH
Kim
Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi, Korea.
Kyung Cho
KC
Cho
Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi, Korea.
Kwang Pyo
KP
Kim
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Yong Kwang
YK
Park
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Sung Hyun
SH
Ahn
Department of Anatomy, School of Medicine, Konkuk University, Seoul, Korea.
Seung Hwa
SH
Park
Department of Surgery, Uijeongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea.
Kee-Hwan
KH
Kim
Department of Internal Medicine, Uijeongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea.
Chang Wook
CW
Kim
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Hong Seok
HS
Kang
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Ah Ram
AR
Lee
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Soree
S
Park
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Heewoo
H
Sim
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Juhee
J
Won
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.
Kieun
K
Seok
Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Korea.
Jueng Soo
JS
You
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Jeong-Hoon
JH
Lee
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Nam-Joon
NJ
Yi
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Kwang-Woong
KW
Lee
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Kyung-Suk
KS
Suh
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Baik L
BL
Seong
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.|KU Open Innovation Center, Konkuk University, Seoul, Korea.|Research Institute of Medical Sciences, Konkuk University, Seoul, Korea.
Kyun-Hwan
KH
Kim
D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D018899:CpG Islands / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D007372:Interferons / Q000276:immunology*; D008099:Liver / Q000378:metabolism; D008745:Methylation; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000096:biosynthesis / Q000235:genetics*; D020543:Proteome; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D000070584:Tripartite Motif Proteins / Q000096:biosynthesis / Q000235:genetics*
D020121:5' Untranslated Regions; D015778:Minor Histocompatibility Antigens; D020543:Proteome; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins; D007372:Interferons
HEPATITIS B; INFECTIOUS DISEASE; LIVER