Nonstructural 5A protein of hepatitis C virus interacts with pyruvate carboxylase and modulates viral propagation

PLoS One. 2013 Jul 4;8(7):e68170. doi: 10.1371/journal.pone.0068170. Print 2013.

Abstract

Hepatitis C virus (HCV) is highly dependent on cellular factors for its own propagation. By employing tandem affinity purification method, we identified pyruvate carboxylase (PC) as a cellular partner for NS5A protein. NS5A interacted with PC through the N-terminal region of NS5A and the biotin carboxylase domain of PC. PC expression was decreased in cells expressing NS5A and HCV-infected cells. Promoter activity of PC was also decreased by NS5A protein. However, FAS expression was increased in cells expressing NS5A and cell culture grown HCV (HCVcc)-infected cells. Silencing of PC promoted fatty acid synthase (FAS) expression level. These data suggest HCV may modulate PC via NS5A protein for its own propagation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Fatty Acid Synthase, Type I / genetics
  • Fatty Acid Synthase, Type I / metabolism*
  • Gene Expression Regulation
  • Hepacivirus / genetics
  • Hepacivirus / metabolism*
  • Hepatocytes / enzymology*
  • Hepatocytes / virology
  • Host-Pathogen Interactions
  • Humans
  • Lipid Metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Pyruvate Carboxylase / genetics
  • Pyruvate Carboxylase / metabolism*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication

Substances

  • NS-5 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • FASN protein, human
  • Fatty Acid Synthase, Type I
  • Pyruvate Carboxylase

Grant support

This work was supported by Basic Science Research Program (2012026351) and Biotechnology Development (2008-2004100) from the Ministry of Education, Science and Technology, Korea, and by the National R&D Program (1020290) for Cancer Control, Ministry for Health and Welfare, Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.