RacGTPase-activating protein 1 interacts with hepatitis C virus polymerase NS5B to regulate viral replication

Ming-Jhan Wu, Po Yuan Ke, Jim Tong Horng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) is a positive-strand RNA virus responsible for chronic liver disease and hepatocellular carcinoma (HCC). RacGTPase-activating protein 1 (RacGAP1) plays an important role during GTP hydrolysis to GDP in Rac1 and CDC42 protein and has been demonstrated to be upregulated in several cancers, including HCC. However, the molecular mechanism leading to the upregulation of RacGAP1 remains poorly understood. Here, we showed that RacGAP1 levels were enhanced in HCV cell-culture-derived (HCVcc) infection. More importantly, we illustrated that RacGAP1 interacts with the viral protein NS5B in mammalian cells. The small interfering RNA (siRNA)-mediated knockdown of RacGAP1 in human hepatoma cell lines inhibited replication of HCV RNA, protein, and production of infectious particles of HCV genotype 2a strain JFH1. Conversely, these were reversed by the expression of a siRNA-resistant RacGAP1 recombinant protein. In addition, viral protein NS5B polymerase activity was significantly reduced by silencing RacGAP1 and, vice versa, was increased by overexpression of RacGAP1 in a cell-based reporter assay. Our results suggest that RacGAP1 plays a crucial role in HCV replication by affecting viral protein NS5B polymerase activity and holds importance for antiviral drug development.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume454
Issue number1
DOIs
StatePublished - Nov 7 2014
Externally publishedYes

Fingerprint

Viruses
Hepacivirus
Proteins
Viral Proteins
Hepatocellular Carcinoma
Small Interfering RNA
rac1 GTP-Binding Protein
Cells
RNA
Hepatitis A
RNA Viruses
Virus Replication
Guanosine Triphosphate
Recombinant Proteins
Antiviral Agents
Cell culture
Liver Diseases
Liver
Hydrolysis
Chronic Disease

Keywords

  • Cell-based reporter assay
  • Hepatitis C virus
  • NS5B polymerase
  • RacGTPase-activating protein 1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

RacGTPase-activating protein 1 interacts with hepatitis C virus polymerase NS5B to regulate viral replication. / Wu, Ming-Jhan; Ke, Po Yuan; Horng, Jim Tong.

In: Biochemical and Biophysical Research Communications, Vol. 454, No. 1, 07.11.2014, p. 19-24.

Research output: Contribution to journalArticle

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