Attenuation stem-loop lesions in the 5' noncoding region of poliovirus RNA: neuronal cell-specific translation defects
Open accessAbstract
The nucleotide at position 480 in the 5' noncoding region of the viral RNA genome plays an important role in directing the attenuation phenotype of the Sabin vaccine strain of poliovirus type 1. In vitro translation studies have shown that the attenuated viral genomes of the Sabin strains direct levels of viral protein synthesis lower than those of their neurovirulent counterparts. We previously described the isolation of pseudorevertant polioviruses derived from transfections of HeLa cells with genome-length RNA harboring an eight-nucleotide lesion in a stem-loop structure (stem-loop V) that contains the attenuation determinant at position 480 (A. A. Haller and B. L. Semler, J. Virol. 66:5075-5086, 1992). This stem-loop structure is a major component of the poliovirus internal ribosome entry site required for initiation of viral protein synthesis. The eight-nucleotide lesion (X472) was lethal for virus growth and gave rise only to viruses which had partially reverted nucleotides within the original substituted sequences. In this study, we analyzed two of the poliovirus revertants (X472RI and X472R2) for cell-type-specific growth properties. The X472RI and X472R2 RNA templates directed protein synthesis to wild-type levels in in vitro translation reaction mixtures supplemented with crude cytoplasmic HeLa cell extracts. In contrast, the same X472 revertant RNAs displayed a decreased translation initiation efficiency when translated in a cell-free system supplemented with extracts from neuronal cells. This translation initiation defect of the X472R templates correlated with reduced yields of infectious virus particles in neuronal cells compared with those obtained from HeLa cells infected with the X472 poliovirus revertants. Our results underscore the important of RNA secondary structures within the poliovirus internal ribosome entry site in directing translation initiation and suggest that such structures interact with neuronal cell factors in a specific manner.
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- Authors
- Haller, A. A., Stewart, S. R., & Semler, B. L.
- Affiliations
- University of California, Irvine (US)
- ORCID
- Semler, B L
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 1996-03
- Volume
- 70
- Issue
- 3
- Pages
- 1467-1474
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC189967
- OpenAlex
- W1535419237
- Cited by
- 70
- References
- 38
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 2
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5t32gm007134-19)
- National Institute of General Medical Sciences (GM-07134)
- National Institute of Allergy and Infectious Diseases (AI-07319, T32AI007319, AI 26765)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- poliovirus type 1, Sabin vaccine strains, attenuation, 5' untranslated region, internal ribosome entry site, translation initiation, RNA secondary structure, HeLa cells, viral protein synthesis
- MeSH terms
- Base Sequence, Defective Viruses, HeLa Cells, Humans, Molecular Sequence Data, Mutation, Neurons, Nucleic Acid Conformation, RNA, Viral, Protein Biosynthesis, Tumor Cells, Cultured, Viral Proteins, Poliovirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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