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World J Gastroenterol. Jun 7, 2018; 24(21): 2261-2268
Published online Jun 7, 2018. doi: 10.3748/wjg.v24.i21.2261
Hepatitis B virus pathogenesis: Fresh insights into hepatitis B virus RNA
Kazuma Sekiba, Motoyuki Otsuka, Motoko Ohno, Mari Yamagami, Takahiro Kishikawa, Tatsunori Suzuki, Rei Ishibashi, Takahiro Seimiya, Eri Tanaka, Kazuhiko Koike
Kazuma Sekiba, Motoyuki Otsuka, Motoko Ohno, Mari Yamagami, Takahiro Kishikawa, Tatsunori Suzuki, Rei Ishibashi, Takahiro Seimiya, Eri Tanaka, Kazuhiko Koike, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Author contributions: Sekiba K, Otsuka M and Ohno M wrote the manuscript; Yamagami M, Kishikawa T, Suzuki T, Ishibashi R, Seimiya T, and Tanaka E prepared the figures; Koike K supervised the entire project.
Supported by the Research Program on Hepatitis from Japan Agency for Medical Research and Development, AMED to Otsuka M, No. JP18fk0210214; and the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED to Otsuka M, No. JP19cm0106602.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
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: Motoyuki Otsuka, MD, PhD, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. otsukamo-tky@umin.ac.jp
Telephone: +81-3-58008812 Fax: +81-3-38140021
Received: March 27, 2018
Peer-review started: March 28, 2018
First decision: April 19, 2018
Revised: April 24, 2018
Accepted: April 26, 2018
Article in press: April 26, 2018
Published online: June 7, 2018
Abstract

Hepatitis B virus (HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host miRNAs and may deregulate miRNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viral-derived miRNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBV-derived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBV-induced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics.

Keywords: Hepatitis B virus, Hepatitis B virus RNA, MicroRNA, Smc5/6, Viral replication, Hepatic fibrosis, Genome integration, Hepatocellular carcinoma

Core tip: Recently, it has been shown that hepatitis B virus (HBV) RNAs have diverse biological functions in the pathogenesis of HBV. HBV RNAs may work as sponges for host miRNAs and deregulate miRNA functions. Novel viral-host fusion RNA may be produced from HBV-DNA integration sites, which may also have pathological functions. Understanding HBV RNA transcription and the biological functions of HBV-related RNAs may open a new avenue for the development of novel HBV therapeutics that target HBV RNAs.