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World J Gastroenterol. Apr 7, 2014; 20(13): 3457-3467
Published online Apr 7, 2014. doi: 10.3748/wjg.v20.i13.3457
How hepatitis C virus invades hepatocytes: The mystery of viral entry
Yong-Zhe Zhu, Xi-Jing Qian, Ping Zhao, Zhong-Tian Qi
Yong-Zhe Zhu, Xi-Jing Qian, Ping Zhao, Zhong-Tian Qi, Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China
Author contributions: All authors contributed to this work.
Supported by Research Grants from National S and T Major Project for Infectious Diseases Control, No. 2012ZX10002003-004-010; National Natural Science Foundation of China, No. 81171564, No. 81273557 and No. 81302812; Medical Youth Science Program, No. 13QNP100; Shanghai Municipal Natural Science Foundation, No. 13ZR1449300; Shanghai LAD Project, No. B901
Correspondence to: Zhong-Tian Qi, PhD, Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. qizt@smmu.edu.cn
Telephone: +86-21-81870988 Fax: +86-21-81870988
Received: September 28, 2011
Revised: December 15, 2013
Accepted: January 3, 2014
Published online: April 7, 2014
Processing time: 187 Days and 17.4 Hours
Abstract

Hepatitis C virus (HCV) infection is a global health problem, with an estimated 170 million people being chronically infected. HCV cell entry is a complex multi-step process, involving several cellular factors that trigger virus uptake into the hepatocytes. The high- density lipoprotein receptor scavenger receptor class B type I, tetraspanin CD81, tight junction protein claudin-1, and occludin are the main receptors that mediate the initial step of HCV infection. In addition, the virus uses cell receptor tyrosine kinases as entry regulators, such as epidermal growth factor receptor and ephrin receptor A2. This review summarizes the current understanding about how cell surface molecules are involved in HCV attachment, internalization, and membrane fusion, and how host cell kinases regulate virus entry. The advances of the potential antiviral agents targeting this process are introduced.

Keywords: Hepatitis C virus; Virus entry; Hepatocytes; Receptor; Host kinase; Antiviral target

Core tip: Cell entry is the first step in viral infection and replication, which offers an important target for antiviral therapy. Hepatitis C virus (HCV) cell entry is a complex multi-step process, involving a several cellular factors that trigger virus uptake into the hepatocytes. This review summarizes the current understanding about how cell surface molecules are involved in HCV attachment, internalization, and membrane fusion, and how host cell kinases regulate virus entry. The advances of the potential antiviral agents targeting this process are introduced.