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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2015; 21(38): 10739-10748
Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10739
Immune and non-immune responses to hepatitis C virus infection
Jiaren Sun, Ricardo Rajsbaum, MinKyung Yi
Jiaren Sun, Ricardo Rajsbaum, MinKyung Yi, Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070, United States
Author contributions: Sun J, Rajsbaum R and Yi M analyzed the literature and wrote the manuscript.
Supported by NIH AI109100 (to Sun J), R01AI110358 (to Yi M); and UTMB Institute for Human Infection and Immunity and UT System Rising STAR Award (to Rajsbaum R).
Conflict-of-interest statement: The authors have no conflict of interest to report.
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: Jiaren Sun, MD, PhD, Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1070, United States. jisun@utmb.edu
Telephone: +1-409-7470186 Fax: +1-409-7476869
Received: May 18, 2015
Peer-review started: May 20, 2015
First decision: June 23, 2015
Revised: July 6, 2015
Accepted: September 14, 2015
Article in press: September 14, 2015
Published online: October 14, 2015
Abstract

The host innate and adaptive immune systems are involved in nearly every step of hepatitis C virus (HCV) infection. In patients, the outcome is determined by a series of complex host-virus interactions, whether it is a natural infection or results from clinical intervention. Strong and persistent CD8+ and CD4+ T-cell responses are critical in HCV clearance, as well as cytokine-induced factors that can directly inhibit virus replication. Newly available direct-acting antivirals (DAAs) are very effective in viral clearance in patients. DAA treatment may further result in the down-regulation of programmed death-1, leading to rapid restoration of HCV-specific CD8+ T cell functions. In this review, we focus on recent studies that address the host responses critical for viral clearance and disease resolution. Additional discussion is devoted to the prophylactic vaccine development as well as to current efforts aimed at understanding the host innate responses against HCV infection. Current theories on how the ubiquitin system and interferon-stimulated genes may affect HCV replication are also discussed.

Keywords: Hepatitis C virus, Hepatitis, T cell, Direct-acting antiviral, Innate immune response

Core tip: Hepatitis C virus (HCV) is an etiologic agent that can cause severe liver diseases, including chronic hepatitis, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Although newly available direct-acting antivirals (DAAs) are very effective in viral clearance in patients, it remains unclear as to how many of the world’s infected individuals will benefit from the new DAAs. In this review, we focus on recent studies that address the host responses critical for viral clearance and disease resolution. Additional discussion is devoted to the prophylactic vaccine development and innate responses against HCV infection. Current theories on how the ubiquitin system and interferon-stimulated genes may affect HCV replication are also discussed.