Investigating the Hepatitis B Virus Life Cycle Using Engineered Reporter Hepatitis B Viruses

Overview

Journal Cancer Sci

Specialty Oncology

Date 2017 Nov 10

PMID 29121422

Citations 11

Authors

Hironori Nishitsuji

Keisuke Harada

Saneyuki Ujino

Jing Zhang

Michinori Kohara

Masaya Sugiyama

Masashi Mizokami

Kunitada Shimotohno

Affiliations

Soon will be listed here.

Abstract

Chronic infection with hepatitis B virus (HBV) increases the risk of developing fibrosis, cirrhosis or hepatocellular carcinoma. Current therapies are limited to type-I interferons and/or nucleos(t)ide analogues; however, these are only partially effective. The development of novel anti-HBV agents for new treatment strategies has been hampered by the lack of a suitable system that allows the in vitro replication of HBV. Studies of virus infection/replication at the molecular level using wild-type HBV are labor-intensive and time-consuming. To overcome these problems, we previously constructed a recombinant reporter HBV bearing the NanoLuc gene and showed its usefulness in identifying factors that affect HBV proliferation. Because this system mimics the early stage of the HBV life cycle faithfully, we conducted a quantitative analysis of HBV infectivity to several human hepatocyte cell lines as well as the effect of dimethyl sulfoxide and HBV protein X on the early stage of HBV proliferation using this system. Furthermore, we developed a system to produce a reporter HBV expressing a pol gene. These reporter HBV may provide an opportunity to enhance our understanding of the HBV life cycle and aid strategies for the development of new anti-HBV agents.

Citing Articles

MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX.

Muchtar A, Onomura D, Ding D, Nishitsuji H, Shimotohno K, Okada S Front Microbiol. 2025; 15:1499216.

PMID: 39834379 PMC: 11743939. DOI: 10.3389/fmicb.2024.1499216.

A decade of liver organoids: Advances in disease modeling.

Liu Y, Sheng J, Yang C, Ding J, Chan Y Clin Mol Hepatol. 2023; 29(3):643-669.

PMID: 36880210 PMC: 10366802. DOI: 10.3350/cmh.2022.0428.

Identification of neutralizing epitopes in the preS2 domain of the hepatitis B virus.

Yato K, Matsuda M, Fukano K, Tanaka T, Moriishi K, Nishitsuji H Virus Res. 2022; 323:199014.

PMID: 36511290 PMC: 10194358. DOI: 10.1016/j.virusres.2022.199014.

Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen.

Washizaki A, Murayama A, Murata M, Kiyohara T, Yato K, Yamada N Nat Commun. 2022; 13(1):5207.

PMID: 36064848 PMC: 9441830. DOI: 10.1038/s41467-022-32910-z.

DNA Engineering and Hepatitis B Virus Replication.

Gan C, Cui J, Zhang W, Wang Y, Huang A, Hu J Front Microbiol. 2021; 12:783040.

PMID: 34858381 PMC: 8632529. DOI: 10.3389/fmicb.2021.783040.

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