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Dual Stem Loops within the Poliovirus Internal Ribosomal Entry Site Control Neurovirulence
Open accessAbstract
In the human central nervous system, susceptibility to poliovirus (PV) infection is largely confined to a specific subpopulation of neuronal cells. PV tropism is likely to be determined by cell-external components such as the PV receptor CD155, as well as cell-internal constraints such as the availability of a suitable microenvironment for virus propagation. We reported previously that the exchange of the cognate internal ribosomal entry site (IRES) within the 5′ nontranslated region of PV with its counterpart from human rhinovirus type 2 (HRV2) can eliminate the neuropathogenic phenotype in a transgenic mouse model for poliomyelitis without diminishing the growth properties in HeLa cells. We now show that attenuation of neurovirulence of PV/HRV2 chimeras is not confined to CD155 transgenic mice but is evident also after intraspinal inoculation into Cynomolgus monkeys. We have dissected the PV and HRV2 IRES elements to determine those structures responsible for neurovirulence (or attenuation) of these chimeric viruses. We report that two adjacent stem loop structures within the IRES cooperatively determine neuropathogenicity.
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“The substitutions in the IRES, which alter stem-loop structures (63, 68, 126, 132) and reduce the efficiency of initiation of translation of the poliovirus RNA template (68, 188), contribute most to the attenuated phenotype of the Sabin 1 and Sabin 3 strains.”
From VACCINE-DERIVED POLIOVIRUSES AND THE ENDGAME STRATEGY FOR GLOBAL POLIO ERADICATION (2005) · cites this paper as [63]
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VACCINE-DERIVED POLIOVIRUSES AND THE ENDGAME STRATEGY FOR GLOBAL POLIO ERADICATION
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Metadata
- Authors
- Gromeier, M., Bossert, B., Arita, M., Nomoto, A., & Wimmer, E.
- Affiliations
- State University of New York (US)
- Institute of Medical Science, The University of Tokyo (JP)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 1999-02
- Volume
- 73
- Issue
- 2
- Pages
- 958-964
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC103915
- OpenAlex
- W1529709430
- Cited by
- 160
- References
- 45
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 8 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 6 · 2015: 4 · 2014: 14 · 2013: 5 · 2012: 4
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI032100, R01AI039485)
- Topics
- Health Sciences › Medicine › Infectious Diseases › 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
- poliovirus, internal ribosome entry site, neurovirulence, stem-loop structure, CD155, 5' untranslated region, neurotropism, viral attenuation, transgenic mouse model, Macaca fascicularis
- MeSH terms
- Animals, Base Sequence, HeLa Cells, Humans, Macaca fascicularis, Membrane Proteins, Mice, Transgenic, Molecular Sequence Data, Neurons, Nucleic Acid Conformation, Receptors, Virus, RNA, Viral, Virulence, Poliovirus, 5' Untranslated Regions, Mice
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