PMID- 16809299
OWN - NLM
STAT- MEDLINE
DCOM- 20060830
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 80
IP  - 14
DP  - 2006 Jul
TI  - The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation 
      initiation at the rhinovirus type 2 internal ribosome entry site.
PG  - 6936-42
AB  - Poliovirus (PV) plus-strand RNA genomes initiate translation in a cap-independent 
      manner via an internal ribosome entry site (IRES) in their 5' untranslated 
      region. Viral translation is codetermined by cellular IRES trans-acting factors, 
      which can influence viral propagation in a cell-type-specific manner. Engineering 
      of a poliovirus recombinant devoid of neuropathogenic properties but highly lytic 
      in malignant glioma cells was accomplished by exchange of the cognate poliovirus 
      IRES with its counterpart from human rhinovirus type 2 (HRV2), generating 
      PV-RIPO. Neuroblast:glioma heterokaryon analyses revealed that loss of 
      neurovirulence is due to trans-dominant repression of PV-RIPO propagation in 
      neuronal cells. The double-stranded RNA binding protein 76 (DRBP76) was 
      previously identified to bind to the HRV2 IRES in neuronal cells and to inhibit 
      PV-RIPO translation and propagation (M. Merrill, E. Dobrikova, and M. Gromeier, 
      J. Virol. 80:3347-3356, 2006). The results of size exclusion chromatography 
      indicate that DRBP76 heterodimerizes with nuclear factor of activated T cells, 45 
      kDa (NF45), in neuronal but not in glioma cells. The DRBP76:NF45 heterodimer 
      binds to the HRV2 IRES in neuronal but not in glioma cells. Ribosomal profile 
      analyses show that the heterodimer preferentially associates with the translation 
      apparatus in neuronal cells and arrests translation at the HRV2 IRES, preventing 
      PV-RIPO RNA assembly into polysomes. Results of this study suggest that the 
      DRBP76:NF45 heterodimer selectively blocks HRV2 IRES-driven translation 
      initiation in neuron-derived cells.
FAU - Merrill, Melinda K
AU  - Merrill MK
AD  - Department of Molecular Genetics & Microbiology, Duke University Medical Center, 
      Box 3020, Durham, NC 27710, USA.
FAU - Gromeier, Matthias
AU  - Gromeier M
LA  - eng
GR  - NS20023/NS/NINDS NIH HHS/United States
GR  - P50 NS020023/NS/NINDS NIH HHS/United States
GR  - CA87537/CA/NCI NIH HHS/United States
GR  - R55 CA087537/CA/NCI NIH HHS/United States
GR  - R01 CA087537/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (5' Untranslated Regions)
RN  - 0 (ILF2 protein, human)
RN  - 0 (Nuclear Factor 45 Protein)
RN  - 0 (RNA, Double-Stranded)
RN  - 0 (RNA, Viral)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - 5' Untranslated Regions/*metabolism
MH  - Cell Line, Tumor
MH  - Chromatography, Gel
MH  - Dimerization
MH  - Glioma/metabolism/virology
MH  - Humans
MH  - Hybridomas
MH  - Neurons/metabolism/virology
MH  - Nuclear Factor 45 Protein/*metabolism
MH  - Organ Specificity
MH  - Polyribosomes/metabolism
MH  - Protein Binding
MH  - Protein Biosynthesis
MH  - RNA, Double-Stranded/*metabolism
MH  - RNA, Viral/*metabolism
MH  - RNA-Binding Proteins/*metabolism
MH  - Rhinovirus/*metabolism/pathogenicity
PMC - PMC1489066
EDAT- 2006/07/01 09:00
MHDA- 2006/08/31 09:00
PMCR- 2006/11/01
CRDT- 2006/07/01 09:00
PHST- 2006/07/01 09:00 [pubmed]
PHST- 2006/08/31 09:00 [medline]
PHST- 2006/07/01 09:00 [entrez]
PHST- 2006/11/01 00:00 [pmc-release]
AID - 80/14/6936 [pii]
AID - 0243-06 [pii]
AID - 10.1128/JVI.00243-06 [doi]
PST - ppublish
SO  - J Virol. 2006 Jul;80(14):6936-42. doi: 10.1128/JVI.00243-06.