Clin Mol Hepatol > Volume 30(3); 2024 > Article
Clinical and Molecular Hepatology 2024;30(3): 539-560.
Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction
Mehrangiz Dezhbord1, Seong Ho Kim1, Soree Park1, Da Rae Lee1, Nayeon Kim1, Juhee Won1,2, Ah Ram Lee1, Dong-Sik Kim3, Kyun-Hwan Kim1
1Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, Korea
2Department of Pharmacology, School of Medicine, Konkuk University, Seoul, Korea
3Department of Surgery, Division of HBP Surgery and Liver Transplantation, College of Medicine, Korea University, Seoul, Korea
Correspondence :  Kyun-Hwan Kim ,
Tel: +82-31-299-6126, Fax: +82-31-299-6029, Email:
Received: January 22, 2024  Revised: May 2, 2024   Accepted: May 13, 2024
*Mehrangiz Dezhbord and Seong Ho Kim contributed equally to this work.
The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells.
Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively.
We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function.
Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.
KeyWords: Hepatitis B virus; MHC class II transactivator; HBV X protein; Interferon-gamma; Hepatocyte nuclear factor

Editorial Office
The Korean Association for the Study of the Liver
Room A1210, 53 Mapo-daero(MapoTrapalace, Dowha-dong), Mapo-gu, Seoul, 04158, Korea
TEL: +82-2-703-0051   FAX: +82-2-703-0071    E-mail:
Copyright © The Korean Association for the Study of the Liver.         
TODAY : 1224
TOTAL : 1926901
Close layer