Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2015; 21(6): 1794-1803
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1794
Occult infection related hepatitis B surface antigen variants showing lowered secretion capacity
Hong Kim, Seoung-Ae Lee, You-Sub Won, HyunJoo Lee, Bum-Joon Kim
Hong Kim, Seoung-Ae Lee, You-Sub Won, HyunJoo Lee, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea
Author contributions: Kim H and Kim BJ conceived this research and participated in its design and coordination; Kim H and Lee SA performed the experiments; Kim H, Lee SA, Won YS, and Lee HJ analyzed and interpreted the data; Lee SA, Won YS, and Lee HJ contributed the reagents, materials, and analysis tools; Kim H and Kim BJ wrote and reviewed the manuscript; all authors approved the final manuscript.
Supported by National Research Foundation of Korea grant funded by the Korean Government (Ministry of Education, Science, and Technology), Grant No. 2013-005810.
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: Bum-Joon Kim, Professor, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul 110-799, South Korea. kbumjoon@snu.ac.kr
Telephone: +82-2-7408316 Fax: +82-2-7430881
Received: June 10, 2014
Peer-review started: June 12, 2014
First decision: July 21, 2014
Revised: July 31, 2014
Accepted: November 7, 2014
Article in press: November 11, 2014
Published online: February 14, 2015
Processing time: 246 Days and 6.1 Hours
Abstract

AIM: To elucidate the molecular mechanisms underlying hepatitis B virus (HBV) occult infection of genotype C.

METHODS: A total of 10 types of hepatitis B surface antigen (HBsAg) variants from a Korean occult cohort were used. After a complete HBV genome plasmid mutated such that it does not express HBsAg and plasmid encoding, each HBsAg variant was transiently co-transfected into HuH-7 cells. The secretion capacity and intracellular expression of the HBV virions and HBsAgs in their respective variants were analyzed using real-time quantitative polymerase chain reaction assays and commercial HBsAg enzyme-linked immunosorbent assays, respectively.

RESULTS: All variants exhibited lower levels of HBsAg secretion into the medium compared with the wild type. In particular, in eight of the ten variants, very low levels of HBsAg secretion that were similar to the negative control were detected. In contrast, most variants (9/10) exhibited normal virion secretion capacities comparable with, or even higher than, the wild type. This provided new insight into the intrinsic nature of occult HBV infection, which leads to HBsAg sero-negativeness but has horizontal infectivity. Furthermore, most variants generated higher reactive oxidative species production than the wild type. This finding provides potential links between occult HBV infection and liver disease progression.

CONCLUSION: The presently obtained data indicate that deficiency in the secretion capacity of HBsAg variants may have a pivotal function in the occult infections of HBV genotype C.

Keywords: Occult infection; Hepatitis B virus; Hepatitis B surface antigen; Variants; Genotype C; Reactive oxidative species

Core tip: The presently obtained data indicate that deficiency in the secretion capacity of hepatitis B surface antigen (HBsAg), but not virion, may have a pivotal function in occult infections of hepatitis B virus (HBV) genotype C, at least in occult infections in South Korea. This provided new insight into the intrinsic nature of HBV occult infections, which lead to HBsAg sero-negativeness but horizontal infectivity. In addition, reactive oxidative species production via possible induction of endoplasmic reticulum stress in hepatocytes provide a probable explanation for the links between occult infection and liver disease progression.