Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2018; 24(10): 1084-1092
Published online Mar 14, 2018. doi: 10.3748/wjg.v24.i10.1084
Sex disparity in viral load, inflammation and liver damage in transgenic mice carrying full hepatitis B virus genome with the W4P mutation in the preS1 region
Seoung-Ae Lee, So-Young Lee, Yu-Min Choi, Hong Kim, Bum-Joon Kim
Seoung-Ae Lee, So-Young Lee, Yu-Min Choi, Hong Kim, Bum-Joon Kim, Department of Microbiology and Immunology, Biomedical Sciences, Liver Research Institute and Cancer Research Institute, Seoul National University, College of Medicine, Seoul 110799, South Korea
Author contributions: Kim BJ conceived this research and participated in its design and coordination; Lee SA performed the experiments; Lee SY, Choi YM and Kim H analyzed and interpreted the data; Kim BJ contributed the reagents, materials and analysis tools.
Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute and the Ministry of Health and Welfare, South Korea, No. HI14C0955.
Conflict-of-interest statement: There was no conflict of interest.
Data sharing statement: No additional data are available.
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:
Correspondence to: Bum-Joon Kim, PhD, Professor, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul 110799, South Korea.
Telephone: +82-2-7408316 Fax: +82-2-7430881
Received: January 11, 2018
Peer-review started: January 11, 2018
First decision: January 25, 2018
Revised: January 31, 2018
Accepted: February 9, 2018
Article in press: February 9, 2018
Published online: March 14, 2018
Core Tip

Core tip: With the development of hepatitis B virus (HBV) vaccine, the rate of chronic HBV infection has dramatically declined worldwide. However, the incidence of hepatocellular carcinoma (HCC), which is characterized by poor prognosis and low survival rate, is on the rise. Predominance in males is a representative global epidemiological characteristic of HCC. Recently, we introduced the novel W4P substitution into the preS1 region, which associated with HCC and notably occurred exclusively in male patients. Our study in the nude mouse xenograft model indicated that the W4P mutation likely contributed to IL-6-dependent HCC progression, particularly in male individuals. Here, to gain further insight into the role of this mutation in HBV-induced liver inflammation, we created transgenic mice carrying the full HBV genome with this mutation. Of note, our data showed that W4P transgene males of 10 mo of age, but not W4P transgene females, spontaneously developed liver damage due to IL-6-mediated liver inflammation, further supporting the previous finding regarding the contribution of the W4P mutation to sex disparity in susceptibility to HCC. Furthermore, our results prove the utility of the developed W4P transgene mouse model for research into the mechanisms of HBV-caused liver diseases.