Hepatitis C Virus entry: the early steps in the viral replication cycle

Ali Sabahi

doi:10.1186/1743-422x-6-117

Abstract

Approximately 170 million are infected with the hepatitis C virus (HCV) world wide and an estimated 2.7 million are HCV RNA positive in the United States alone. The acute phase of the HCV infection, in majority of individuals, is asymptomatic. A large percentage of those infected with HCV are unable to clear the virus and become chronically infected. The study of the HCV replication cycle was hampered due to difficulties in growing and propagating the virus in an in vitro setting. The advent of the HCV pseudo particle (HCVpp) and HCV cell culture (HCVcc) systems have made possible the study of the HCV replication cycle, in vitro. Studies utilizing the HCVpp and HCVcc systems have increased our insight into the early steps of the viral replication cycle of HCV, such as the identification of cellular co-receptors for binding and entry. The aim of this article is to provide a review of the outstanding literature on HCV entry, specifically looking at cellular co-receptors involved and putting the data in the context of the systems used (purified viral envelope proteins, HCVpp system, HCVcc system and/or patient sera) and to also give a brief description of the cellular co-receptors themselves.

Highlights

Epidemiology Approximately 170 million are infected with the hepatitis C virus (HCV) world wide
In retrospective studies in individuals with chronic HCV infections, cirrhosis of the liver occurred in 17–55%, hepatocellular carcinoma (HCC) developed in 1–23%, and liver related death occurred in 4–15%
A decrease of HCV cell culture (HCVcc) cholesterol levels led to a decrease in the infectivity of the virus [100]. These results indicate the importance in cholesterol levels to infectivity which further highlight the role SRBI plays directly and indirectly in HCV infection

Summary

Introduction

Epidemiology Approximately 170 million are infected with the hepatitis C virus (HCV) world wide. Claudin-1 is expressed in all hepatoma cell lines permissive to HCVcc and HCVpp infection, except for Bel7402 [112], as well as primary hepatocytes [113]. HCVpp infection of 293T cells expressing claudin-1 was inhibited by serum from HCV+ patients, anti-CD81, and bafilomycin A1, demonstrating http://www.virologyj.com/content/6/1/117 that HCVpp entry was dependent on the envelope glycoproteins, CD81, and endosomal acidification [113]. Treatment of hepatocytes with monoclonal antibodies against LDLR or LDL inhibited HCV infection [26] These findings and the association of HCV particles with lipoproteins suggest a role for LDLR as a cellular receptor for HCV. Overexpression of human OCLN in HCV resistant cell lines, which express the other entry co-receptors, led specific enhancement in susceptibility to HCVpp infection. Claudin 1 and SRBI co-localization was seen at the basolateral membrane in both normal and HCV infected liver tissue

Conclusion

Levrero M

Brown RS

Findings

72. Hemler ME