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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2015; 21(24): 7400-7411
Published online Jun 28, 2015. doi: 10.3748/wjg.v21.i24.7400
Applications of human hepatitis B virus preS domain in bio- and nanotechnology
Riki Toita, Takahito Kawano, Jeong-Hun Kang, Masaharu Murata
Riki Toita, Department of Biomaterials, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
Takahito Kawano, Masaharu Murata, Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Takahito Kawano, Masaharu Murata, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan
Jeong-Hun Kang, Division of Biopharmaceutics and Pharmacokinetics, Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka 565-8565, Japan
Author contributions: Toita R, Kawano T, Kang JH and Murata M contributed to the design of this manuscript; Kang JH and Murata M critically checked and revised the manuscript; all authors participated in writing the manuscript.
Supported by Health Labour Sciences Research Grant (Research on Publicly Essential Drugs and Medical Devices) from the Ministry of Health, Labour and Welfare of Japan, a Special Coordination Funds for Promoting Science and Technology (SCF funding program “Innovation Center for Medical Redox Navigation”), a Grant-in Aid for Scientific Research, No. 24300172 and for Young-Scientists, No. 25750176 from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Fukuoka Foundation for Sound Health Cancer Research Fund.
Conflict-of-interest: The authors report 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: Masaharu Murata, Professor, Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. m-murata@dem.med.kyushu-u.ac.jp
Telephone: +81-92-6426251 Fax: +81-92-6426252
Received: January 22, 2015
Peer-review started: January 24, 2015
First decision: February 10, 2015
Revised: February 24, 2015
Accepted: May 2, 2015
Article in press: May 4, 2015
Published online: June 28, 2015
Abstract

Human hepatitis B virus (HBV) is a member of the family Hepadnaviridae, and causes acute and chronic infections of the liver. The hepatitis B surface antigen (HBsAg) contains the large (L), middle (M), and small (S) surface proteins. The L protein consists of the S protein, preS1, and preS2. In HBsAg, the preS domain (preS1 + preS2) plays a key role in the infection of hepatocytic cells by HBV and has several immunogenic epitopes. Based on these characteristics of preS, several preS-based diagnostic and therapeutic materials and systems have been developed. PreS1-specific monoclonal antibodies (e.g., MA18/7 and KR127) can be used to inhibit HBV infection. A myristoylated preS1 peptide (amino acids 2-48) also inhibits the attachment of HBV to HepaRG cells, primary human hepatocytes, and primary tupaia hepatocytes. Antibodies and antigens related to the components of HBsAg, preS (preS1 + preS2), or preS1 can be available as diagnostic markers of acute and chronic HBV infections. Hepatocyte-targeting delivery systems for therapeutic molecules (drugs, genes, or proteins) are very important for increasing the clinical efficacy of these molecules and in reducing their adverse effects on other organs. The selective delivery of diagnostic molecules to target hepatocytic cells can also improve the efficiency of diagnosis. In addition to the full-length HBV vector, preS (preS1 + preS2), preS1, and preS1-derived fragments can be useful in hepatocyte-specific targeting. In this review, we discuss the literature concerning the applications of the HBV preS domain in bio- and nanotechnology.

Keywords: Hepatitis B virus, Hepatocyte, Delivery system, Vaccine, Hepatitis B surface antigen, Diagnosis

Core tip: The hepatitis B surface antigen (HBsAg) of human hepatitis B virus (HBV) contains the large (L), middle (M), and small (S) surface proteins. The L protein consists of the S protein, preS1, and preS2. In HBsAg, the preS domain (preS1 + preS2) plays a key role in the infection of hepatocytic cells by HBV and has several immunogenic epitopes. Therefore, the preS domain can act as a diagnostic or therapeutic target or as material for developing inhibitors of HBV infection, HBV vaccines, diagnostic tools for HBV infection, and hepatocyte-targeting delivery systems for diagnostic or therapeutic molecules.