Casein kinase II inhibitor enhances production of infectious genotype 1a hepatitis C virus (H77S)

PLoS One. 2014 Dec 2;9(12):e113938. doi: 10.1371/journal.pone.0113938. eCollection 2014.

Abstract

Genotype 2a JFH1 virus has substantially contributed to the progress of HCV biology by allowing entire viral life cycle of HCV in cell culture. Using this genotype 2a virus, casein kinase II (CKII) was previously identified as a crucial host factor in virus assembly by phosphorylating NS5A. Since most of the prior studies employed genotype 2a JFH1 or JFH1-based intragenotypic chimera, we used genotype 1a H77S to study virus assembly. CKII inhibition by chemical inhibitors enhanced H77S virus production in contrast to that of JFH1 virus, but genetic inhibition of CKII by siRNA did not change H77S virus titer significantly. The different outcomes from these two approaches of CKII inhibition suggested that nonspecific target kinase of CKII inhibitors plays a role in increasing H77S virus production and both viral and host factors were investigated in this study. Our results emphasize substantial differences among the HCV genotypes that should be considered in both basic research and clinical practices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Benzimidazoles / pharmacology
  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / chemistry
  • Casein Kinase II / genetics
  • Cell Line
  • Cinnamates / pharmacology
  • Genotype*
  • Hepacivirus / genetics*
  • Hepacivirus / pathogenicity
  • Humans
  • Molecular Sequence Data
  • RNA Interference
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Virus Replication / drug effects

Substances

  • 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole
  • Antiviral Agents
  • Benzimidazoles
  • Cinnamates
  • Viral Nonstructural Proteins
  • Viral Proteins
  • tetrabromocinnamic acid
  • Casein Kinase II
  • NS-5 protein, hepatitis C virus

Grants and funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2008346). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.