The hepatitis C virus life cycle as a target for new antiviral therapies

Gastroenterology. 2007 May;132(5):1979-98. doi: 10.1053/j.gastro.2007.03.116.

Abstract

The burden of disease consequent to hepatitis C virus (HCV) infection has been well described and is expected to increase dramatically over the next decade. Current approved antiviral therapies are effective in eradicating the virus in approximately 50% of infected patients. However, pegylated interferon and ribavirin-based therapy is costly, prolonged, associated with significant adverse effects, and not deemed suitable for many HCV-infected patients. As such, there is a clear and pressing need for the development of additional agents that act through alternate or different mechanisms, in the hope that such regimens could lead to enhanced response rates more broadly applicable to patients with hepatitis C infection. Recent basic science enhancements in HCV cell culture systems and replication assays have led to a broadening of our understanding of many of the mechanisms of HCV replication and, therefore, potential novel antiviral targets. In this article, we have attempted to highlight important new information as it relates to our understanding of the HCV life cycle. These steps broadly encompass viral attachment, entry, and fusion; viral RNA translation; posttranslational processing; HCV replication; and viral assembly and release. In each of these areas, we present up-to-date knowledge of the relevant aspects of that component of the viral life cycle and then describe the preclinical and clinical development targets and pathways being explored in the translational and clinical settings.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepacivirus / physiology*
  • Hepatitis C / drug therapy*
  • Humans
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / physiology
  • RNA, Viral / genetics
  • Virus Assembly / drug effects
  • Virus Assembly / physiology
  • Virus Attachment / drug effects
  • Virus Replication / drug effects
  • Virus Replication / physiology

Substances

  • Antiviral Agents
  • RNA, Viral