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World J Gastroenterol. Jun 21, 2014; 20(23): 7104-7122
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7104
Production and pathogenicity of hepatitis C virus core gene products
Hui-Chun Li, Hsin-Chieh Ma, Chee-Hing Yang, Shih-Yen Lo
Hui-Chun Li, Department of Biochemistry, Tzu Chi University, Hualien 97004, Taiwan
Hsin-Chieh Ma, Chee-Hing Yang, Shih-Yen Lo, Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien 97004, Taiwan
Shih-Yen Lo, Department of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan
Author contributions: Lo SY designed research; Ma HC performed research; Li HC, Yang CH and Lo SY wrote the paper.
Supported by Grants from the National Science Council of Taiwan, NSC 101-2320-B-320-011 to Lo SY and from the Tzu Chi University, TCMRC-P-101015 and TCRPP101017 to Li HC and Lo SY
Correspondence to: Shih-Yen Lo, Professor, Department of Laboratory Medicine and Biotechnology, Tzu Chi University, 701, Section 3, Chung Yang Road, Hualien 97004, Taiwan. losylo@mail.tcu.edu.tw
Telephone: +886-3-8565301-2320 Fax: +886-3-8571917
Received: September 28, 2013
Revised: December 5, 2013
Accepted: April 1, 2014
Published online: June 21, 2014
Abstract

Hepatitis C virus (HCV) is a major cause of chronic liver diseases, including steatosis, cirrhosis and hepatocellular carcinoma, and its infection is also associated with insulin resistance and type 2 diabetes mellitus. HCV, belonging to the Flaviviridae family, is a small enveloped virus whose positive-stranded RNA genome encoding a polyprotein. The HCV core protein is cleaved first at residue 191 by the host signal peptidase and further cleaved by the host signal peptide peptidase at about residue 177 to generate the mature core protein (a.a. 1-177) and the cleaved peptide (a.a. 178-191). Core protein could induce insulin resistance, steatosis and even hepatocellular carcinoma through various mechanisms. The peptide (a.a. 178-191) may play a role in the immune response. The polymorphism of this peptide is associated with the cellular lipid drop accumulation, contributing to steatosis development. In addition to the conventional open reading frame (ORF), in the +1 frame, an ORF overlaps with the core protein-coding sequence and encodes the alternative reading frame proteins (ARFP or core+1). ARFP/core+1/F protein could enhance hepatocyte growth and may regulate iron metabolism. In this review, we briefly summarized the current knowledge regarding the production of different core gene products and their roles in viral pathogenesis.

Keywords: Hepatitis C virus, Core protein, Alternative reading frame/core+1 proteins, Insulin resistance, Steatosis, Hepatocellular carcinoma, Interferon

Core tip: In addition to the mature core protein (a.a. 1-177) and the cleaved peptide (a.a. 178-191), different alternative reading frame (ARF)/core+1 proteins could be expressed from the core+1 reading frame of hepatitis C virus (HCV) core gene. Core gene products play an important role in the HCV pathogenesis. Core protein could induce insulin resistance, steatosis, and even hepatocellular carcinoma. The peptide (a.a. 178-191) may play a role in the immune response and steatosis development. ARF proteins/core+1/F protein could enhance hepatocyte growth and may regulate iron metabolism. We summarized the current knowledge regarding the HCV core gene products and their pathogenicity in this article.