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

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

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
2
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, USA.
3
Department of Microbial Pathogenesis, Yale University, New Haven, Connecticut, USA.
4
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, USA Department of Chemistry, Yale University, New Haven, Connecticut, USA Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA anna.pyle@yale.edu.

Abstract

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.

PMID:
24965468
PMCID:
PMC4178846
DOI:
10.1128/JVI.00745-14
[Indexed for MEDLINE]
Free PMC Article

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