Evolution of the Sabin type 1 poliovirus in humans: characterization of strains isolated from patients with vaccine-associated paralytic poliomyelitis

Georgescu, M M; Balanant, J; Macadam, A; Otelea, D; Combiescu, M; Combiescu, A A; Crainic, R; Delpeyroux, F

doi:10.1128/jvi.71.10.7758-7768.1997

Cited by 83Viral Infections and Immunology ResearchVirology and Viral DiseasesEvolution and Genetic Dynamics

Evolution of the Sabin type 1 poliovirus in humans: characterization of strains isolated from patients with vaccine-associated paralytic poliomyelitis

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Georgescu, M M, Balanant, J, Macadam, A, Otelea, D, Combiescu, M, Combiescu, A A, Crainic, R, Delpeyroux, F·1997·Journal of Virology

DOI 10.1128/jvi.71.10.7758-7768.1997PMC PMC192128

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Abstract

Attenuated strains of the Sabin oral poliovirus vaccine replicate in the human gut and in rare cases cause vaccine-associated paralytic poliomyelitis (VAPP). Reversion of vaccine strains toward a pathogenic phenotype is probably one of the main causes of VAPP, a disease most frequently associated with type 3 and type 2 strains and more rarely with the type 1 (Sabin 1) strain. To identify the determinants and mechanisms of safety versus pathogenicity of the Sabin 1 strain, we characterized the genetic and phenotypic changes in six Sabin 1-derived viruses isolated from immunocompetent patients with VAPP. The genomes of these strains carried either few or numerous mutations from the original Sabin 1 genome. As assessed in transgenic mice carrying the human poliovirus receptor (PVR-Tg mice), all but one strain had lost the attenuated phenotype. Four strains presented only a moderate neurovirulent phenotype, probably due at least in part to reversions to the wild-type genotype, which were detected in the 5' noncoding region of the genome. The reversions found in most strains at nucleotide position 480, are known to be associated with an increase in neurovirulence. The construction and characterization of Sabin 1 mutants implicated a reversion at position 189, found in one strain, in the phenotypic change. The presence of 71 mutations in one neurovirulent strain suggests that a vaccine-derived strain can survive for a long time in humans. Surprisingly, none of the strains analyzed were as neurovirulent to PVR-Tg mice as was the wild-type parent of Sabin 1 (Mahoney) or a previously identified neurovirulent Sabin 1 mutant selected at a high temperature in cultured cells. Thus, in the human gut, the Sabin 1 strain does not necessarily evolve toward the genetic characteristics and high neuropathogenicity of its wild-type parent.

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Authors: Georgescu, M. M., Balanant, J., Macadam, A., Otelea, D., Combiescu, M., Combiescu, A. A., Crainic, R., & Delpeyroux, F.
Affiliations: Institut Pasteur (FR)
Epidémiologie Moléculaire des Entérovirus, Institut Pasteur, Paris, France.
ORCID: Macadam, A
Delpeyroux, F
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 1997-10
Volume: 71
Issue: 10
Pages: 7758-7768
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.71.10.7758-7768.1997
PMC: PMC192128
OpenAlex: W2125016488
Cited by: 83
References: 67
Citations by year: 2025: 1 · 2024: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 3
FWCI: 1.70
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords: vaccine-associated paralytic poliomyelitis, oral polio vaccine, neurovirulence, attenuated phenotype, Mahoney strain, vaccine-derived poliovirus
MeSH terms: Animals, Base Sequence, Genotype, Humans, Phenotype, Poliomyelitis, Poliovirus Vaccine, Oral, RNA, Viral, Serotyping, Tumor Cells, Cultured, Virulence, Virus Replication, Poliovirus, Mice

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Evolution of the Sabin type 1 poliovirus in humans: characterization of strains isolated from patients with vaccine-associated paralytic poliomyelitis

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