The linker region of NS3 plays a critical role in the replication and infectivity of hepatitis C virus

J Virol. 2014 Sep;88(18):10970-4. doi: 10.1128/JVI.00745-14. Epub 2014 Jun 25.


Hepatitis C virus (HCV) NS3-4A is required for viral replication and assembly. We establish that virus assembly is sensitive to mutations in the linker region between the helicase and protease domains of NS3-4A. However, we find that the protease cleavage, RNA binding, and unwinding rates of NS3 are minimally affected in vitro. Thus, we conclude that the NS3 linker is critical for mediating protein-protein interactions and dynamic control rather than for modulating the enzymatic functions of NS3-4A.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Hepacivirus / chemistry
  • Hepacivirus / enzymology*
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Hepatitis C / virology*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Protein Binding
  • Sequence Alignment
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • NS3 protein, hepatitis C virus
  • NS4A cofactor peptide, Hepatitis C virus
  • Viral Nonstructural Proteins

Associated data

  • PDB/3O8C