The 5′ noncoding region of the type 2 poliovirus vaccine strain contains determinants of attenuation and temperature sensitivity

Macadam, Andrew I.; Pollard, Stuart; Ferguson, Geraldine; Dunn, Glynis; Skuce, Robin; Almond, Jeffrey W.; Minor, Philip D.

doi:10.1016/0042-6822(91)90877-e

Cited by 98 publications

(70 citation statements)

References 17 publications

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“…The latter results reflect primarily the temperature-sensitive phenotype (see below), which in Sabin 2 is largely determined by A 481 (91).…”

Section: Figmentioning

confidence: 85%

“…Higher virus yields at elevated temperatures may facilitate person-to-person transmission by increasing the amount of infectious virus excreted by febrile individuals. Sabin 2, all 25 VDPV2 isolates tested, and MEF-1 grew to high titers (8.23 to 9.42 log 10 PFU/ml) in RD cells incubated at 37.0°C when measured by plaque assays on L20B cells also incubated at 37.0°C (Table 5) (73,91). However, when cells were incubated at 39.5°C for plaque assays, the efficiency of plating of Sabin 2 on L20B cells dropped Ն6,000-fold, whereas that of MEF-1 was largely unaltered.…”

Section: Figmentioning

confidence: 99%

See 1 more Smart Citation

Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

Burns

Shaw

Jorba

et al. 2013

J Virol

141

161

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“…The latter results reflect primarily the temperature-sensitive phenotype (see below), which in Sabin 2 is largely determined by A 481 (91).…”

Section: Figmentioning

confidence: 85%

Section: Figmentioning

confidence: 99%

Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

Burns

Shaw

Jorba

et al. 2013

J Virol

141

161

View full text Add to dashboard Cite

“…The results of the assay show that the two most mutated PV2/PV1 recombinants had lost their temperature sensitivity and behaved as wild-type strains. The basis for this was seen in the 59 NCR of the genome, where nt 481, considered responsible for attenuation and temperature sensitivity (Macadam et al, 1991;Ren et al, 1991), had reverted back to wild-type. However, this change was seen in all PV2/PV1 recombinant strains and in PV2-31996, isolated 1 week after the first dose of OPV.…”

Section: Discussionmentioning

confidence: 99%

Comparison of poliovirus recombinants: accumulation of point mutations provides further advantages

Savolainen-Kopra

Самойлович

Kahelin

et al. 2009

Journal of General Virology

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The roles of recombination and accumulation of point mutations in the origin of new poliovirus (PV) characteristics have been hypothesized, but it is not known which are essential to evolution. We studied phenotypic differences between recombinant PV strains isolated from successive stool specimens of an oral PV vaccine recipient. The studied strains included three PV2/PV1 recombinants with increasing numbers of mutations in the VP1 gene, two of the three with an amino acid change IAT in the DE-loop of VP1, their putative PV1 parent and strains Sabin 1 and 2. Growth of these viruses was examined in three cell lines: colorectal adenocarcinoma, neuroblastoma and HeLa. The main observation was a higher growth rate between 4 and 6 h post-infection of the two recombinants with the IAT substitution. All recombinants grew at a higher rate than parental strains in the exponential phase of the replication cycle. In a temperature sensitivity test, the IATsubstituted recombinants replicated equally well at an elevated temperature. Complete genome sequencing of the three recombinants revealed 12 (3), 19 (3) and 27 (3) nucleotide (amino acid) differences from Sabin. Mutations were located in regions defining attenuation, temperature sensitivity, antigenicity and the cis-acting replicating element. The recombination site was in the 59 end of 3D. In a competition assay, the most mutated recombinant beat parental Sabin in all three cell lines, strongly suggesting that this virus has an advantage. Two independent intertypic recombinants, PV3/PV1 and PV3/PV2, also showed similar growth advantages, but they also contained several point mutations. Thus, our data defend the hypothesis that accumulation of certain advantageous mutations plays a key role in gaining increased fitness.

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“…HEp2C, BGM, and Vero cells were grown in monolayers as described previously (22). L20B cells (mouse L cells expressing the human poliovirus receptor) were grown as previously described (31).…”

Section: Methodsmentioning

confidence: 99%

Rational Design of Genetically Stable, Live-Attenuated Poliovirus Vaccines of All Three Serotypes: Relevance to Poliomyelitis Eradication

Macadam

Ferguson

Stone

et al. 2006

J Virol

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The global eradication of poliomyelitis caused by wild-type virus is likely to be completed within the next few years, despite immense logistic and political difficulties, and may ultimately be followed by the cessation of vaccination. However, the existing live-attenuated vaccines have the potential to revert to virulence, causing occasional disease, and viruses can be shed by immunocompromised individuals for prolonged periods of time. Moreover, several outbreaks of poliomyelitis have been shown to be caused by viruses derived from the Sabin vaccine strains. The appearance of such strains depends on the prevailing circumstances but poses a severe obstacle to strategies for stopping vaccination. Vaccine strains that are incapable of reversion at a measurable rate would provide a possible solution. Here, we describe the constructions of strains of type 3 poliovirus that are stabilized by the introduction of four mutations in the 5 noncoding region compared to the present vaccine. The strains are genetically and phenotypically stable under conditions where the present vaccine loses the attenuating mutation in the 5 noncoding region completely. Type 1 and type 2 strains in which the entire 5 noncoding regions of Sabin 1 and Sabin 2 were replaced exactly with that of one of the type 3 strains were also constructed. The genetic stability of 5 noncoding regions of these viruses matched that of the type 3 strains, but significant phenotypic reversion occurred, illustrating the potential limitations of a rational approach to the genetic stabilization of live RNA virus vaccines.Poliomyelitis is caused by poliovirus, a member of the picornavirus family that occurs in three serotypes such that immunity to one serotype does not protect against the other two.

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The 5′ noncoding region of the type 2 poliovirus vaccine strain contains determinants of attenuation and temperature sensitivity

Cited by 98 publications

References 17 publications

Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

Comparison of poliovirus recombinants: accumulation of point mutations provides further advantages

Rational Design of Genetically Stable, Live-Attenuated Poliovirus Vaccines of All Three Serotypes: Relevance to Poliomyelitis Eradication

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