PMID- 19889774
OWN - NLM
STAT- MEDLINE
DCOM- 20100112
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 84
IP  - 2
DP  - 2010 Jan
TI  - Host and viral translational mechanisms during cricket paralysis virus infection.
PG  - 1124-38
LID - 10.1128/JVI.02006-09 [doi]
AB  - The dicistrovirus is a positive-strand single-stranded RNA virus that possesses 
      two internal ribosome entry sites (IRES) that direct translation of distinct open 
      reading frames encoding the viral structural and nonstructural proteins. Through 
      an unusual mechanism, the intergenic region (IGR) IRES responsible for viral 
      structural protein expression mimics a tRNA to directly recruit the ribosome and 
      set the ribosome into translational elongation. In this study, we explored the 
      mechanism of host translational shutoff in Drosophila S2 cells infected by the 
      dicistrovirus, cricket paralysis virus (CrPV). CrPV infection of S2 cells results 
      in host translational shutoff concomitant with an increase in viral protein 
      synthesis. CrPV infection resulted in the dissociation of eukaryotic translation 
      initiation factor 4G (eIF4G) and eIF4E early in infection and the induction of 
      deIF2alpha phosphorylation at 3 h postinfection, which lags after the initial 
      inhibition of host translation. Forced dephosphorylation of deIF2alpha by 
      overexpression of dGADD34, which activates protein phosphatase I, did not prevent 
      translational shutoff nor alter virus production, demonstrating that deIF2alpha 
      phosphorylation is dispensable for host translational shutoff. However, premature 
      induction of deIF2alpha phosphorylation by thapsigargin treatment early in 
      infection reduced viral protein synthesis and replication. Finally, translation 
      mediated by the 5' untranslated region (5'UTR) and the IGR IRES were resistant to 
      impairment of eIF4F or eIF2 in translation extracts. These results support a 
      model by which the alteration of the deIF4F complex contribute to the shutoff of 
      host translation during CrPV infection, thereby promoting viral protein synthesis 
      via the CrPV 5'UTR and IGR IRES.
FAU - Garrey, Julianne L
AU  - Garrey JL
AD  - Department of Biochemistry, 5457-2350 Health Sciences Mall, University of British 
      Columbia, Vancouver, BC V6T 1Z3, Canada.
FAU - Lee, Yun-Young
AU  - Lee YY
FAU - Au, Hilda H T
AU  - Au HH
FAU - Bushell, Martin
AU  - Bushell M
FAU - Jan, Eric
AU  - Jan E
LA  - eng
GR  - MOP-81244/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091104
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - 0 (Insect Proteins)
RN  - 0 (Viral Proteins)
RN  - 0 (eIF4E1 protein, Drosophila)
RN  - 0 (eIF4G2 protein, Drosophila)
RN  - EC 2.7.11.1 (PERK kinase)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - 5' Untranslated Regions/genetics
MH  - Animals
MH  - Cells, Cultured
MH  - Dicistroviridae/*pathogenicity
MH  - Drosophila/cytology/*virology
MH  - Drosophila Proteins/genetics/metabolism
MH  - Eukaryotic Initiation Factor-4E/genetics/metabolism
MH  - Eukaryotic Initiation Factor-4G/genetics/metabolism
MH  - Gene Expression Regulation
MH  - *Host-Pathogen Interactions
MH  - Insect Proteins/genetics/*metabolism
MH  - *Protein Biosynthesis
MH  - Ribosomes/genetics/metabolism
MH  - Viral Proteins/genetics/*metabolism
MH  - eIF-2 Kinase/genetics/metabolism
PMC - PMC2798387
EDAT- 2009/11/06 06:00
MHDA- 2010/01/13 06:00
PMCR- 2010/07/01
CRDT- 2009/11/06 06:00
PHST- 2009/11/06 06:00 [entrez]
PHST- 2009/11/06 06:00 [pubmed]
PHST- 2010/01/13 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - JVI.02006-09 [pii]
AID - 2006-09 [pii]
AID - 10.1128/JVI.02006-09 [doi]
PST - ppublish
SO  - J Virol. 2010 Jan;84(2):1124-38. doi: 10.1128/JVI.02006-09. Epub 2009 Nov 4.