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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2016; 22(31): 7017-7029
Published online Aug 21, 2016. doi: 10.3748/wjg.v22.i31.7017
Roles of hepatocyte nuclear factors in hepatitis B virus infection
Doo Hyun Kim, Hong Seok Kang, Kyun-Hwan Kim
Doo Hyun Kim, Hong Seok Kang, Kyun-Hwan Kim, Department of Pharmacology, and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 143-701, South Korea
Kyun-Hwan Kim, KU Open Innovation Center, Konkuk University, Seoul 143-701, South Korea
Kyun-Hwan Kim, Research Institute of Medical Science, Konkuk University, Seoul 143-701, South Korea
Author contributions: Kim DH and Kang HS contributed equally to this work; Kim DH, Kang HS and Kim KH analyzed the literature and wrote the manuscript.
Supported by Konkuk University in 2016.
Conflict-of-interest statement: No conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Kyun-Hwan Kim, Department of Pharmacology, School of Medicine, Konkuk University, Seoul 143-701, South Korea. khkim10@kku.ac.kr
Telephone: +82-2-20307833 Fax: +82-2-20496192
Received: March 29, 2016
Peer-review started: April 5, 2016
First decision: May 12, 2016
Revised: June 2, 2016
Accepted: June 28, 2016
Article in press: June 29, 2016
Published online: August 21, 2016
Abstract

Approximately 350 million people are estimated to be persistently infected with hepatitis B virus (HBV) worldwide. HBV maintains persistent infection by employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs. Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide analogs such as lamivudine, adefovir, entecavir, and tenofovir. However, these treatments rarely cure CHB because they are unable to inhibit cccDNA transcription and inhibit only a late stage in the HBV life cycle (the reverse transcription step in the nucleocapsid). Therefore, an understanding of the factors regulating cccDNA transcription is required to stop this process. Among numerous factors, hepatocyte nuclear factors (HNFs) play the most important roles in cccDNA transcription, especially in the generation of viral genomic RNA, a template for HBV replication. Therefore, proper control of HNF function could lead to the inhibition of HBV replication. In this review, we summarize and discuss the current understanding of the roles of HNFs in the HBV life cycle and the upstream factors that regulate HNFs. This knowledge will enable the identification of new therapeutic targets to cure CHB.

Keywords: Hepatitis B virus, Hepatocyte nuclear factor, Covalently closed circular DNA, Replication

Core tip: Hepatitis B virus (HBV) infection is the leading cause of chronic liver disease and death worldwide. Persistent HBV infection is a major risk factor for chronic hepatitis and is the leading cause of liver disease, including cirrhosis and hepatocellular carcinoma. In the HBV life cycle, hepatocyte nuclear factors (HNFs) play critical roles in covalently closed circular DNA transcription. Control of HNF expression and function could regulate HBV replication. Therefore, understanding the upstream cellular factors or signals involved in the regulation of HNFs is important for controlling HBV replication.