Molecular Mechanisms of Attenuation of the Sabin Strain of Poliovirus Type 3
Open accessAbstract
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.
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In Sabin 3, the critical C472U substitution reduces the efficiency of binding of the PTB, required for initiation of translation, to the IRES.
“In Sabin 3, the critical C472U substitution reduces the efficiency of binding of the PTB, required for initiation of translation, to the IRES (65).”
From VACCINE-DERIVED POLIOVIRUSES AND THE ENDGAME STRATEGY FOR GLOBAL POLIO ERADICATION (2005) · cites this paper as [65]
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VACCINE-DERIVED POLIOVIRUSES AND THE ENDGAME STRATEGY FOR GLOBAL POLIO ERADICATION
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- Authors
- Guest, S., Pilipenko, E., Sharma, K., Chumakov, K., & Roos, R. P.
- Affiliations
- Committee on Microbiology
- Department of Neurobiology, Pharmacology, and Physiology
- Center for Biologics Evaluation and Research (US)
- University of Chicago (US)
- Corresponding author
- Roos, Raymond P.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2004-10-15
- Volume
- 78
- Issue
- 20
- Pages
- 11097-11107
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC521805
- OpenAlex
- W2115181164
- Cited by
- 101
- References
- 53
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 5
- FWCI
- 4.14
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- poliovirus type 3, Sabin vaccine strains, viral attenuation, internal ribosome entry site, polypyrimidine tract-binding protein, central nervous system, attenuating mutations, RNA-binding proteins
- MeSH terms
- Animals, Binding Sites, Cell Line, Chick Embryo, Cricetinae, HeLa Cells, Humans, Mutation, Neurons, Poliovirus Vaccine, Oral, Ribosomes, Spinal Cord, Protein Biosynthesis, Virulence, Poliovirus, Electroporation, Polypyrimidine Tract-Binding Protein
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