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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 18, 2016; 8(17): 716-725
Published online Jun 18, 2016. doi: 10.4254/wjh.v8.i17.716
Innate immune targets of hepatitis B virus infection
Zhi-Qiang Zou, Li Wang, Kai Wang, Ji-Guang Yu
Zhi-Qiang Zou, Li Wang, Ji-Guang Yu, Infectious Disease Hospital of Yantai, Yantai 264001, Shandong Province, China
Kai Wang, Hepatology Department, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Zou ZQ, Wang L and Yu JG performed literature search; Wang L and Wang K designed and wrote manuscript.
Conflict-of-interest statement: All the authors of the manuscript declare that they have no conflict of interest in connection with this paper.
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: Li Wang, PhD, Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai 264001, Shandong Province, China. liliwang2200@163.com
Telephone: +86-535-6232253 Fax: +86-535-6628542
Received: March 25, 2016
Peer-review started: March 25, 2016
First decision: April 19, 2016
Revised: May 19, 2016
Accepted: June 1, 2016
Article in press: June 3, 2016
Published online: June 18, 2016
Processing time: 81 Days and 5.4 Hours
Abstract

Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.

Keywords: Hepatitis B virus; Infection; Targets; Innate immune response; Signaling pathway

Core tip: The pathogenesis of hepatitis B virus (HBV) infection is initiated and driven by complicated interplays between the virus and the host immune system. HBV DNA and different HBV proteins have various effects on different arms of innate immune system. The extent of HBV replication as well as the amounts of circulating HBV antigens and different source of HBV proteins have heterogenous effects on innate immune responses and antiviral signaling pathways. Other factors, such as liver inflammation may also have impact on innate immune response. Multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.