An N-terminal amphipathic helix in hepatitis C virus (HCV) NS4B mediates membrane association, correct localization of replication complex proteins, and HCV RNA replication. Academic Article uri icon

Overview

abstract

  • Like other positive-strand RNA viruses, hepatitis C virus (HCV) is believed to replicate its RNA in association with host cell cytoplasmic membranes. Because of its association with such membranes, NS4B, one of the virus's nonstructural proteins, may play an important role in this process, although the mechanistic details are not well understood. We identified a putative N-terminal amphipathic helix (AH) in NS4B that mediates membrane association. Introduction of site-directed mutations designed to disrupt the hydrophobic face of the AH abolishes the AH's ability to mediate membrane association. An AH in NS4B is conserved across HCV isolates. Completely disrupting the amphipathic nature of NS4B's N-terminal helix abolished HCV RNA replication, whereas partial disruption resulted in an intermediate level of replication. Finally, immunofluorescence studies revealed that HCV replication complex components were mislocalized in the AH-disrupted mutant. These results identify a key membrane-targeting domain which can form the basis for developing novel antiviral strategies.

publication date

  • October 1, 2004

Research

keywords

  • Cell Membrane
  • Gene Expression Regulation, Viral
  • Hepacivirus
  • RNA, Viral
  • Replicon
  • Viral Nonstructural Proteins

Identity

PubMed Central ID

  • PMC521809

Scopus Document Identifier

  • 4644281168

Digital Object Identifier (DOI)

  • 10.1128/JVI.78.20.11393-11400.2004

PubMed ID

  • 15452261

Additional Document Info

volume

  • 78

issue

  • 20