PMID- 21835792
OWN - NLM
STAT- MEDLINE
DCOM- 20111107
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 85
IP  - 20
DP  - 2011 Oct
TI  - Rab5 and class III phosphoinositide 3-kinase Vps34 are involved in hepatitis C 
      virus NS4B-induced autophagy.
PG  - 10561-71
LID - 10.1128/JVI.00173-11 [doi]
AB  - 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.
FAU - Su, Wen-Chi
AU  - Su WC
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
FAU - Chao, Ti-Chun
AU  - Chao TC
FAU - Huang, Yih-Leh
AU  - Huang YL
FAU - Weng, Shih-Che
AU  - Weng SC
FAU - Jeng, King-Song
AU  - Jeng KS
FAU - Lai, Michael M C
AU  - Lai MM
LA  - eng
PT  - Journal Article
DEP - 20110810
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Mutant Proteins)
RN  - 0 (NS4B protein, flavivirus)
RN  - 0 (Viral Nonstructural Proteins)
RN  - EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases)
RN  - EC 3.6.5.2 (rab5 GTP-Binding Proteins)
SB  - IM
MH  - *Autophagy
MH  - Cell Line
MH  - Class III Phosphatidylinositol 3-Kinases/*metabolism
MH  - Gene Silencing
MH  - Hepacivirus/*pathogenicity
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Immunoprecipitation
MH  - Mutant Proteins/metabolism
MH  - Protein Binding
MH  - Viral Nonstructural Proteins/*metabolism
MH  - rab5 GTP-Binding Proteins/antagonists & inhibitors/genetics/*metabolism
PMC - PMC3187495
EDAT- 2011/08/13 06:00
MHDA- 2011/11/08 06:00
PMCR- 2012/04/01
CRDT- 2011/08/13 06:00
PHST- 2011/08/13 06:00 [entrez]
PHST- 2011/08/13 06:00 [pubmed]
PHST- 2011/11/08 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - JVI.00173-11 [pii]
AID - 0173-11 [pii]
AID - 10.1128/JVI.00173-11 [doi]
PST - ppublish
SO  - J Virol. 2011 Oct;85(20):10561-71. doi: 10.1128/JVI.00173-11. Epub 2011 Aug 10.