Hepatitis C virus RNA replication requires a conserved structural motif within the transmembrane domain of the NS5B RNA-dependent RNA polymerase

J Virol. 2010 Nov;84(21):11580-4. doi: 10.1128/JVI.01519-10. Epub 2010 Aug 25.


Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), the viral RNA-dependent RNA polymerase (RdRp), is a tail-anchored protein with a highly conserved C-terminal transmembrane domain (TMD) that is required for the assembly of a functional replication complex. Here, we report that the TMD of the HCV RdRp can be functionally replaced by a newly identified analogous membrane anchor of the GB virus B (GBV-B) NS5B RdRp. Replicons with a chimeric RdRp consisting of the HCV catalytic domain and the GBV-B membrane anchor replicated with reduced efficiency. Compensatory amino acid changes at defined positions within the TMD improved the replication efficiency of these chimeras. These observations highlight a conserved structural motif within the TMD of the HCV NS5B RdRp that is required for RNA replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Conserved Sequence
  • Hepacivirus / genetics*
  • Protein Structure, Tertiary
  • RNA, Viral / biosynthesis*
  • RNA-Dependent RNA Polymerase
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / physiology*


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