Approaches to the Development of New Poliovirus Vaccines Based on Molecular Genetics

Nomoto, Akio; Toyoda, Haruka; Kataoka, Yutaka; Kohara, Michinori; Suganuma, Toshiyuki; Omata, Toshiko; Imura, Nobumasa

doi:10.1093/clinids/6.supplement_2.s494

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…The wide antigenic diversity among the enteroviruses would predict that the conserved sequences were largely located in nontranslated areas of the enteroviral genomes. These observations are substantiated by recently published data of Nomoto et al (11), demonstrating a highly conserved region among the three poliovirus types between nucleotides 400 and 650. Stanway et al (15) have shown absolute homology between bases 509 and 573 of polioviruses 1 and 3.…”

supporting

confidence: 73%

Use of subgenomic poliovirus DNA hybridization probes to detect the major subgroups of enteroviruses

Rotbart¹,

Levin²,

Villarreal³

1984

J Clin Microbiol

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Three nucleic acid hybridization probes were derived from DNA clones of the poliovirus type 1 genome. Used in dot hybridization experiments, the probes successfully detected members of each of the major enteroviral subgroups. The hybridization patterns obtained with the three probes suggested that a highly conserved nucleotide sequence existed among the enteroviruses tested, mapping between bases 220 and 1809 in the poliovirus genome. Two new antiviral agents capable of inhibiting enterovirus replication in tissue culture were used to demonstrate the specificity of the probes for viral RNA. * Corresponding author. saline (30 mM Tris and 150 mM NaCl [pH 7.0]), and the cells were lysed with 0.125 ml of 0.5% Nonidet P-40 (Bethesda Research Laboratories, Gaithersburg, Md.) in Tris-saline. The plates were then scraped, and the cell lysate was centrifuged at 15,000 x g at 4°C for 5 min. Samples of the supernatant fluid were immediately frozen at-70°C. For some experiments, 1 .g (final concentration) of candidate

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supporting

confidence: 73%

Use of subgenomic poliovirus DNA hybridization probes to detect the major subgroups of enteroviruses

Rotbart¹,

Levin²,

Villarreal³

1984

J Clin Microbiol

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“…Region 743 to 1122 harbors only one nucleotide difference between Mahoney and Sabin 1, resulting in one amino acid change in VP4 (Ala-*Ser [24]). The amino acid at this position (residue 65) in VP4, an internal polypeptide of the virion (4, 18, 43) of both the Sabin 2 and Sabin 3 strains, is Ala and is thus the same as that of the virulent Mahoney strain (26,40). On the basis of these considerations, the one amino acid difference in VP4 between Mahoney and Sabin 1 may contribute little to phenotypes of virulence or attenuation, although this will have to be tested with more recombinants.…”

Section: Monkey Neurovirulence Tests On Recombinant Virusesmentioning

confidence: 99%

Genetic analysis of the attenuation phenotype of poliovirus type 1

Omata¹,

Kohara²,

Kuge³

et al. 1986

J Virol

180

138

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Seven different recombinant viruses from the virulent Mahoney and the attenuated Sabin parental strains of type 1 poliovirus were constructed in vitro by using infectious cDNA clones. Monkey neurovirulence tests (lesion score, spread value, and incidence of paralysis) using these recombinant viruses revealed that the loci influencing attenuation were spread over several areas of the viral genome, including the 5' noncoding region. In vitro phenotypic marker tests corresponding to temperature sensitivity of growth (rct marker), plaque size, and dependency of growth on bicarbonate concentration (d marker) were performed to identify the genomic loci of these determinants and to investigate their correlation with attenuation. Determinants of temperature sensitivity mapped to many areas of the viral genome and expressed strong but not perfect correlation with attenuation. Recombinant viruses with Sabin-derived capsid proteins showed a small-plaque phenotype, and their growth was strongly dependent on bicarbonate concentration, suggesting that these determinants map to the genomic region encoding the viral capsid proteins. Plaque size and the d marker, however, were found to be poor indicators of attenuation. Moreover, virion surface characteristics such as immunogenicity and antigenicity had little or no correlation with neurovirulence. Nevertheless, viruses carrying Sabin-derived capsid proteins had an apparent tendency to exhibit less neurovirulence in tests on monkeys compared with recombinants carrying Mahoney-derived capsid proteins. Our results suggest that the extent of viral multiplication in the central nervous system of the test animals might be one of the most important factors determining neurovirulence. Moreover, we conclude that the expression of the attenuated phenotype of the Sabin 1 strain of poliovirus is the result of several different biological characteristics. Finally, none of the in vitro phenotypic markers alone can serve as a good indicator of neurovirulence or attenuation.

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“…If the attenuation of a virus is the result of cumulative mutations, as is the ease for the Sabin vaccine strain of polio virus type 1 (Baltimore, 1984;Nomoto et al, 1984) or the deletion of a significant portion of essential genetic material, e.g. the pseudorabies attenuated vaccines (Lomniczi et al, 1984a,b), then the vaccine may be thought of as 'crippled' and therefore unlikely to revert to the original wild form.…”

Section: Killed and Live Virus Vaccinesmentioning

confidence: 99%

Animal viruses of economic importance: Genetic variation, persistence, and prospects for their control

Hudson

1985

Pharmacology & Therapeutics

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Approaches to the Development of New Poliovirus Vaccines Based on Molecular Genetics

Cited by 6 publications

References 14 publications

Use of subgenomic poliovirus DNA hybridization probes to detect the major subgroups of enteroviruses

Use of subgenomic poliovirus DNA hybridization probes to detect the major subgroups of enteroviruses

Genetic analysis of the attenuation phenotype of poliovirus type 1

Animal viruses of economic importance: Genetic variation, persistence, and prospects for their control

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