Amphipathic helix-dependent localization of NS5A mediates hepatitis C virus RNA replication

J Virol. 2003 May;77(10):6055-61. doi: 10.1128/jvi.77.10.6055-6061.2003.

Abstract

We identified an N-terminal amphipathic helix (AH) in one of hepatitis C virus (HCV)'s nonstructural proteins, NS5A. This AH is necessary and sufficient for membrane localization and is conserved across isolates. Genetically disrupting the AH impairs HCV replication. Moreover, an AH peptide-mimic inhibits the membrane association of NS5A in a dose-dependent manner. These results have exciting implications for the HCV life cycle and novel antiviral strategies.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Membrane / virology
  • Conserved Sequence
  • Gene Expression Regulation, Viral*
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Humans
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • RNA, Viral / biosynthesis*
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication*

Substances

  • Peptides
  • RNA, Viral
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus