Identification of a lipid kinase as a host factor involved in hepatitis C virus RNA replication

Virology. 2009 Apr 25;387(1):5-10. doi: 10.1016/j.virol.2009.02.039. Epub 2009 Mar 21.

Abstract

A functional screen of an adenovirus-delivered shRNA library that targets approximately 4500 host genes was performed to identify cellular factors that regulate hepatitis C virus (HCV) sub-genomic RNA replication. Seventy-three hits were further examined by siRNA oligonucleotide-directed knockdown, and silencing of the PI4KA gene was demonstrated to have a significant effect on the replication of a HCV genotype 1b replicon. Using transient siRNA oligonucleotide transfections and stable shRNA knockdown clones in HuH-7 cells, the PI4KA gene was shown to be essential for the replication of all HCV genotypes tested (1a, 1b and 2a) but not required for bovine viral diarrhea virus (BVDV) RNA replication.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Adenoviridae / physiology
  • Cell Line, Tumor
  • Gene Expression Regulation, Viral
  • Gene Knockdown Techniques
  • Gene Library
  • Genome, Viral
  • Hepacivirus / genetics
  • Hepacivirus / growth & development
  • Hepacivirus / metabolism
  • Hepacivirus / physiology*
  • Hepatitis C / enzymology*
  • Humans
  • Minor Histocompatibility Antigens
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • RNA, Small Interfering / metabolism
  • RNA, Viral / genetics*
  • Reproducibility of Results
  • Virus Replication / genetics*

Substances

  • Minor Histocompatibility Antigens
  • RNA, Small Interfering
  • RNA, Viral
  • Phosphotransferases (Alcohol Group Acceptor)
  • phosphatidylinositol phosphate 4-kinase