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World J Gastroenterol. Apr 7, 2015; 21(13): 3786-3800
Published online Apr 7, 2015. doi: 10.3748/wjg.v21.i13.3786
Hepatitis C virus and antiviral innate immunity: Who wins at tug-of-war?
Da-Rong Yang, Hai-Zhen Zhu
Da-Rong Yang, Hai-Zhen Zhu, Department of Molecular Medicine of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, Hunan Province, China
Hai-Zhen Zhu, Research Center of Cancer Prevention and Treatment, Translational Medicine Research Center of Liver Cancer, Hunan Provincial Tumor Hospital (Affiliated Tumor Hospital of Xiangya Medical School of Central South University), Changsha 410013, Hunan Province, China
Author contributions: Yang DR wrote the paper; Zhu HZ and Yang DR revised the paper.
Conflict-of-interest: The authors declare no conflict 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: Hai-Zhen Zhu, Department of Molecular Medicine of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Yuelushan, Changsha 410082, Hunan Province, China. zhuhaizhen69@yahoo.com
Telephone: +86-731-88821385 Fax: +86-731-88821385
Received: November 27, 2014
Peer-review started: November 28, 2014
First decision: January 8, 2015
Revised: January 21, 2015
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: April 7, 2015
Abstract

Hepatitis C virus (HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon (IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes (ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection.

Keywords: Hepatitis C virus, Interferon, Interferon-stimulated gene, RIG-I, Toll-like receptor, Virus-host interaction, Chronic hepatitis, Immune evasion, Cell culture system for hepatitis C virus

Core tip: The complex interaction between hepatitis C virus (HCV) and its host determines which side the balance tends to be tipped between antiviral innate response and viral immune evasion. The development of new cell culture systems and small animal models for HCV research permits increased understanding of how the host responds to viral infection and what leads to HCV evasion of innate immunity. Recent discoveries in these areas reveal many pivotal factors imparting the control of viral-induced innate immunity, and facilitate the development of novel drugs and effective vaccines for HCV infection.