Cited by 140Viral Infections and Immunology ResearchVirology and Viral DiseasesAnimal Virus Infections Studies

Determinants of attenuation and temperature sensitivity in the type 1 poliovirus Sabin vaccine

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Bouchard, M J, Lam, D H, Racaniello, V R·1995·Journal of Virology

Abstract

To identify determinants of attenuation in the poliovirus type 1 Sabin vaccine strain, a series of recombinant viruses were constructed by using infectious cDNA clones of the virulent type 1 poliovirus P1/Mahoney and the attenuated type 1 vaccine strain P1/Sabin. Intracerebral inoculation of these viruses into transgenic mice which express the human receptor for poliovirus identified regions of the genome that conferred reduced neurovirulence. Exchange of smaller restriction fragments and site-directed mutagenesis were used to identify the nucleotide changes responsible for attenuation. P1/Sabin mutations at nucleotides 935 of VP4, 2438 of VP3, and 2795 and 2879 of VP1 were all shown to be determinants of attenuation. The recombinant viruses and site-directed mutants were also used to identify the nucleotide changes which are involved in the temperature sensitivity of P1/Sabin. Determinants of this phenotype in HeLa cells were mapped to changes at nucleotides 935 of VP4, 2438 of VP3, and 2741 of VP1. The 3Dpol gene of P1/Sabin, which contains three amino acid differences from its parent P1/Mahoney, also contributes to the temperature sensitivity of P1/Sabin; however, mutants containing individual amino acid changes grew as well as P1/Mahoney at elevated temperatures, suggesting that either some combination or all three changes are required for temperature sensitivity. In addition, the 3'-noncoding region of P1/Sabin augments the temperature-sensitive phenotype conferred by 3Dpol. Although nucleotide 2741, 3Dpol, and the 3'-noncoding region of P1/Sabin contribute to the temperature sensitivity of P1/Sabin, they do not contribute to attenuation in transgenic mice expressing the poliovirus receptor, demonstrating that determinants of attenuation and temperature sensitivity can be genetically separated.

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Crossref · 10.1128/jvi.69.8.4972-4978.1995

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Authors
Bouchard, M. J., Lam, D. H., & Racaniello, V. R.
Affiliations
Columbia University Irving Medical Center (US)
Venue
Journal of Virology
Published
1995-08
Volume
69
Issue
8
Pages
4972-4978
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
OpenAlex
W2104799220
Cited by
140
References
50
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2021: 1 · 2020: 5 · 2018: 6 · 2017: 1 · 2016: 3 · 2015: 8 · 2014: 5 · 2013: 2 · 2012: 5
FWCI
6.43
Type
journal article
Language
en
Open access
Locations
  • Journal of Virology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (AI20017)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
poliovirus type 1, Sabin vaccine strains, temperature sensitivity, neurovirulence, VP4, VP3, VP1, 3' non-coding region, poliovirus receptor, transgenic mice, site-directed mutagenesis, recombinant virus
MeSH terms
Animals, Capsid, Female, Hot Temperature, HeLa Cells, Humans, Male, Mice, Transgenic, Nervous System Diseases, Poliovirus Vaccine, Oral, Recombination, Genetic, Vaccines, Attenuated, Virulence, Mutagenesis, Site-Directed, Poliovirus, Mice

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