PMID- 15452230
OWN - NLM
STAT- MEDLINE
DCOM- 20041102
LR  - 20220309
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 78
IP  - 20
DP  - 2004 Oct
TI  - Molecular mechanisms of attenuation of the Sabin strain of poliovirus type 3.
PG  - 11097-107
AB  - Mutations critical for the central nervous system (CNS) attenuation of the Sabin 
      vaccine strains of poliovirus (PV) are located within the viral internal ribosome 
      entry site (IRES). We examined the interaction of the IRESs of PV type 3 (PV3) 
      and Sabin type 3 (Sabin3) with polypyrimidine tract-binding protein (PTB) and a 
      neural cell-specific homologue, nPTB. PTB and nPTB were found to bind to a site 
      directly adjacent to the attenuating mutation, and binding at this site was less 
      efficient on the Sabin3 IRES than on the PV3 IRES. Translation mediated by the 
      PV3 and Sabin3 IRESs in neurons of the chicken embryo spinal cord demonstrated a 
      translation deficit for the Sabin3 IRES that could be rescued by increasing PTB 
      expression in the CNS. These data suggest that the low levels of PTB available in 
      the CNS, coupled to a reduced binding of PTB on the Sabin3 IRES, leads to its 
      CNS-specific attenuation. This study also demonstrates the use of the chicken 
      embryo to easily investigate translation of RNA within a neuron in the CNS of an 
      intact living organism.
FAU - Guest, Stephen
AU  - Guest S
AD  - Department of Neurology, Biological Sciences Division, University of Chicago, 
      5841 S. Maryland Ave., Chicago, IL 60637, USA.
FAU - Pilipenko, Evgeny
AU  - Pilipenko E
FAU - Sharma, Kamal
AU  - Sharma K
FAU - Chumakov, Konstantin
AU  - Chumakov K
FAU - Roos, Raymond P
AU  - Roos RP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Poliovirus Vaccine, Oral)
RN  - 139076-35-0 (Polypyrimidine Tract-Binding Protein)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Chick Embryo
MH  - Cricetinae
MH  - Electroporation
MH  - HeLa Cells
MH  - Humans
MH  - Mutation
MH  - Neurons/metabolism
MH  - Poliovirus/*genetics/*pathogenicity/physiology
MH  - Poliovirus Vaccine, Oral/*genetics
MH  - Polypyrimidine Tract-Binding Protein/genetics/metabolism
MH  - Protein Biosynthesis
MH  - Ribosomes/metabolism
MH  - Spinal Cord
MH  - Virulence/genetics
PMC - PMC521805
EDAT- 2004/09/29 05:00
MHDA- 2004/11/04 09:00
PMCR- 2004/10/01
CRDT- 2004/09/29 05:00
PHST- 2004/09/29 05:00 [pubmed]
PHST- 2004/11/04 09:00 [medline]
PHST- 2004/09/29 05:00 [entrez]
PHST- 2004/10/01 00:00 [pmc-release]
AID - 78/20/11097 [pii]
AID - 0323-04 [pii]
AID - 10.1128/JVI.78.20.11097-11107.2004 [doi]
PST - ppublish
SO  - J Virol. 2004 Oct;78(20):11097-107. doi: 10.1128/JVI.78.20.11097-11107.2004.