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Cited by 330Viral Infections and Immunology ResearchRNA and protein synthesis mechanismsVirology and Viral Diseases

Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants.

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Gromeier, M, Alexander, L, Wimmer, E·1996·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.93.6.2370PMC PMC39803
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Abstract

Neuropathogenicity of poliovirus can be attenuated by mutations in the internal ribosomal entry site (IRES) within the 5' nontranslated region of its genome. The Sabin vaccine strains used in prevention of poliomyelitis carry such mutations in their IRES elements. In addition, mutations within the structural and nonstructural proteins of Sabin strains may equally contribute to the attenuation phenotype. Despite their effectiveness as vaccines, the Sabin strains retain a neuropathogenic potential in animal models for poliomyelitis and, at a very low rate, they can cause poliomyelitis in vaccine recipients. The elimination of the neurocytopathic phenotype was achieved through the exchange of the entire poliovirus IRES with its counterpart from human rhinovirus type 2 without affecting growth properties in nonneuronal cells. The attenuating effect of the human rhinovirus type 2 IRES within the context of a poliovirus genome has been mapped to the 3' portion of this genetic element.

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Research works printed but not linked: 10

  1. [12]Hambidge, S. J. & Sarnow, P. (1992) Proc. Natl. Acad. Sci. USA 89, 10272–10276.
  2. [11]Hellen, C. U. T., Withereli, G. W., Schmid, M., Shin, S. H., Pestova, T. V., Gil, A. & Wimmer, E. (1993) Proc. Natl. Acad. Sci. USA 90, 7642–7646.
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Authors
Gromeier, M., Alexander, L., & Wimmer, E.
Affiliations
  • State University of New York (US)
  • National Institutes of Health (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1996-03-19
Volume
93
Issue
6
Pages
2370-2375
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.93.6.2370
PMC
PMC39803
OpenAlex
W1987977026
Cited by
330
References
29
Citations by year
2026: 3 · 2025: 11 · 2024: 13 · 2023: 19 · 2022: 17 · 2021: 16 · 2020: 14 · 2019: 10 · 2018: 15 · 2017: 10 · 2016: 13 · 2015: 8 · 2014: 13 · 2013: 6 · 2012: 8
FWCI
6.67
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (P01CA028146, CA-28146)
  • National Institute of Allergy and Infectious Diseases (AI-15122, R01AI032100, R01AI-32100)
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
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
internal ribosome entry site, poliovirus, neurovirulence, poliomyelitis, Sabin vaccine strains, 5' untranslated region, attenuation
MeSH terms
Animals, Base Sequence, Cells, Cultured, Humans, Molecular Sequence Data, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Peptide Chain Initiation, Translational, Ribosomes, RNA, Messenger, RNA, Viral, Gene Expression Regulation, Viral, Poliovirus, Mice

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