JBC Thematic Series Explores Hepatitis C Virus

BY NICK ZAGORSKI


The JBC recently unveiled a new thematic minireview series to showcase some of the recent advances in understanding the hepatitis C virus.

Hepatitis C virus is a member of the hepacivirus viral group and the causative agent of hepatitis C, an infectious disease affecting as many as 180 million people worldwide, and a major contributor to chronic liver diseases, including cirrhosis and hepatocellular carcinoma. Although much has been learned about how HCV replicates and how the virus is transmitted, it remains problematic from a therapeutic standpoint. Unlike the related HBV, there is no effective vaccine against HCV, and the present treatment for HCV infection, a regimen of pegylated interferon alpha and the antiviral drug ribavirin, shows varying success rates of 40–80 percent, depending on HCV genotype.

Recently, though, researchers have made significant advances in understanding HCV biochemistry, its life cycle and its interaction with hosts, which may lead to improved treatments and an effective vaccine. To showcase some of these important new findings, the Journal of Biological Chemistry recently presented a thematic review series titled “Hepatitis C Virus-host Interactions.”

This minireview series, coordinated by JBC Associate Editor Charles E. Samuel of the University of California, Santa Barbara, appeared in the May 10 issue of the journal and is collectively available online.

The series consists of five minireviews, two of which appeared in the JBC in previous years but provide an important foundation for the newer studies. The first is a 2006 review by Ralf Bartenschlager and colleagues titled “From Structure to Function: New Insights into Hepatitis C Virus RNA Replication.” The paper describes structural and biochemical insights into HCV RNA replication gained from HCV replicon systems and other methods allowing for efficient propagation of infectious HCV in tissue culture. The subsequent development of a cell-culture system that permitted the complete replication of HCV provided a tool to biochemically delineate the initial processes in infection, namely virion attachment and entry. These advances are described in the 2008 review by Thomas von Hahn and Charles M. Rice entitled “Hepatitis C Viral Entry.”

In the first of the three new minireviews, titled “Hepatitis C Virus Non-structural Protein 3 (HCV NS3): a Multifunctional Antiviral Target,” Craig E. Cameron and colleagues discuss new developments in the biochemistry and structural biology of the bifunctional NS3 protein, which possesses both serine protease activity (in the N-terminal region) and RNA helicase activity (in the C-terminal region). The second new minireview, written by Daniel M Jones and John McLauchlan and titled “Hepatitis C Virus: Assembly and Release of Virus Particles,” summarizes progress in understanding HCV protein trafficking and the various stages of virion assembly and release. The third and final minireview is by Stanley M. Lemon. Titled “Induction and Evasion of Innate Antiviral Responses to Hepatitis C Virus,” this article summarizes the progress in understanding the cellular signaling pathways and antiviral responses antagonized by HCV proteins and the multiple strategies utilized by HCV to evade activated innate antiviral responses.

Together, these five minireviews provide a comprehensive overview of the current state of HCV research and should be a valuable resource to all.

Nick Zagorski (nzagorski@asbmb.org) is a science writer at ASBMB.

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