Cited by 160Viral Infections and Immunology ResearchRNA and protein synthesis mechanismsVirology and Viral Diseases

Dual Stem Loops within the Poliovirus Internal Ribosomal Entry Site Control Neurovirulence

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Gromeier, Matthias, Bossert, Birgit, Arita, Mineo, Nomoto, Akio, Wimmer, Eckard·1999·Journal of Virology

Abstract

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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Crossref · 10.1128/jvi.73.2.958-964.1999

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  • Substitutions in the IRES contribute most to the attenuated phenotype of the Sabin 1 and Sabin 3 strains.

    “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.”

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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
Published
1999-02
Volume
73
Issue
2
Pages
958-964
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
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
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 › 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
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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