Rab5 and class III phosphoinositide 3-kinase Vps34 are involved in hepatitis C virus NS4B-induced autophagy

J Virol. 2011 Oct;85(20):10561-71. doi: 10.1128/JVI.00173-11. Epub 2011 Aug 10.


Autophagy has been shown to facilitate replication or production of hepatitis C virus (HCV); nevertheless, how HCV induces autophagy remains unclear. Here, we demonstrate that HCV nonstructural protein 4B (NS4B) alone can induce autophagy signaling; amino acid residues 1 to 190 of NS4B are sufficient for this induction. Further studies showed that the phosphorylation levels of S6K and 4E-BP1 were not altered, suggesting that the mTOR/S6 kinase pathway and mTOR/4E-BP1 pathway did not contribute to NS4B- or HCV-induced autophagy. Inhibition of Rab5 function by silencing Rab5 or overexpressing dominant-negative Rab5 mutant (S34N) resulted in significant reduction of NS4B- or HCV-induced autophagic vesicle formation. Moreover, the autophagy induction was impaired by inhibition of class III phosphoinositide 3-kinase (PI 3-kinase) Vps34 function. Finally, the coimmunoprecipitation assay indicated that NS4B formed a complex with Rab5 and Vps34, supporting the notion that Rab5 and Vps34 are involved in NS4B-induced autophagy. Taken together, these results not only reveal a novel role of NS4B in autophagy but also offer a clue to the mechanism of HCV-induced autophagy.

MeSH terms

  • Autophagy*
  • Cell Line
  • Class III Phosphatidylinositol 3-Kinases / metabolism*
  • Gene Silencing
  • Hepacivirus / pathogenicity*
  • Host-Pathogen Interactions*
  • Humans
  • Immunoprecipitation
  • Mutant Proteins / metabolism
  • Protein Binding
  • Viral Nonstructural Proteins / metabolism*
  • rab5 GTP-Binding Proteins / antagonists & inhibitors
  • rab5 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / metabolism*


  • Mutant Proteins
  • NS4B protein, flavivirus
  • Viral Nonstructural Proteins
  • Class III Phosphatidylinositol 3-Kinases
  • rab5 GTP-Binding Proteins