Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 6, 2018; 6(9): 233-241
Published online Sep 6, 2018. doi: 10.12998/wjcc.v6.i9.233
Hepatitis B virus-persistent infection and innate immunity defect: Cell-related or virus-related?
Jian Tang, Zhen-Yu Wu, Rong-Juan Dai, Jing Ma, Guo-Zhong Gong
Jian Tang, Zhen-Yu Wu, Jing Ma, Guo-Zhong Gong, Department of Infectious Disease, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Rong-Juan Dai, Department of Infectious Disease, the First Affiliated Hospital of University of South China, Hengyang 421001, Hunan Province, China
Author contributions: Tang J, Wu ZY and Gong GZ wrote the manuscript; Dai RJ and Ma J performed critical revision and editing of the manuscript; all authors gave approval of the final version.
Supported by Natural Science Foundation of China, No. 81500455.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
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: Guo-Zhong Gong, PhD, Professor, Department of Infectious Disease, the Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China.
Telephone: +86-731-85292105 Fax: +86-731-85292173
Received: April 3, 2018
Peer-review started: April 3, 2018
First decision: May 29, 2018
Revised: July 31, 2018
Accepted: August 6, 2018
Article in press: August 7, 2018
Published online: September 6, 2018

The outcomes of hepatitis B virus (HBV) infection are closely related to the age at which infection was acquired. Infection acquired in adult life tends to be self-limited, in contrast to perinatal acquirement, for which chronic persistence of the HBV is a general outcome. Innate immunity plays an indispensable role in early virus infection, facilitating virus clearance. However, it has been reported that HBV is under-recognized and poorly eliminated by the innate immune system in the early stages of infection, possibly explaining the long-lasting persistence of viremia afterwards. Furthermore, due to the existence of covalently closed circular DNA, chronic HBV clearance is very difficult, even when patients are given interferon-α and nucleotide/nucleoside analogs for antiviral therapy. The mechanism by which HBV evades innate immune recognition and establishes persistent infection remains a subject of debate. Besides, some researchers are becoming more interested in how to eradicate chronic HBV infection by restoring or boosting innate immunity. This review aimed to summarize the current knowledge on how intrahepatocyte signaling pathways and innate immune cells act after the onset of HBV infection and how these actions are related to the persistence of HBV. We anticipate the insights presented herein to be helpful for future development of novel immune therapeutic strategies to fight HBV infection.

Keywords: Hepatitis B virus, Innate immunity, Immune evasion, Pattern recognition receptor, Toll-like receptor, Natural killer cells, Kupffer cells, Dendritic cells

Core tip: This review covers the following core concepts of hepatitis B virus (HBV) persistence, according to the most up-to-date literature: Hepatocytes lack immune responsiveness to HBV; Innate immune cells display weak responses at the early stages of HBV infection; HBV impairs functions of innate immune cells and select signaling pathways to evade immune recognition and response.