Reversion of the attenuated and temperature-sensitive phenotypes of the sabin type 3 strain of poliovirus in vaccinees

Macadam, Andrew; Arnold, Caroline; Howlett, J.; John, A.; Marsden, S.A.; Taffs, F.; Reeve, P.; Hamada, Nobuyuki; Wareham, K A; Almond, J. W.; Cammack, N.; Minor, Philip D.

doi:10.1016/0042-6822(89)90183-9

Cited by 121 publications

(107 citation statements)

References 15 publications

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“…This strain showed some reduction in the replication efficiency at elevated temperatures. Furthermore, both PV3 recombinants had the corresponding reversion at nt 472, considered to be responsible for temperature sensitivity and neurovirulence (Macadam et al, 1989;Minor et al, 1989;Westrop et al, 1989). Besides the reversion of the attenuation-defining nucleotide, all studied strains also had other point mutations in the 59 NCR, possibly contributing to the increased fitness.…”

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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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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“…Genetic change in poliovirus can also occur by molecular recombination (Cooper, 1977;Lai, 1992). Genetic recombination of poliovirus vaccine (Sabin) strains has been demonstrated (Kew & Nottay, 1984;Macadam et al, 1989;Lipskaya et al, 1991) and is even frequent (Furione et al, 1993) in strains isolated from vaccine-associated paralytic poliomyelitis cases (VAPP). Viral donors for the recombined genotypes described were of vaccine origin.…”

Section: Maria-magdalena Georgescu* Francis Delpeyroux and Radu Crainicmentioning

confidence: 99%

“…The first is that it contains a recombination junction in the 5' extremity of the genome and, to our knowledge, this is the first report of this phenomenon. Generally, the recombination junctions, whether single (Lipskaya et al, 1991) or multiple (Cammack et al, 1988;Macadam et al, 1989;Georgescu et al, 1994) for natural poliovirus recombinants map in the nonstructural coding region of the viral genome. Here we show that poliovirus can recombine in the 5' extremity and not only in the nonstructural proteincoding region.…”

Section: Hpalimentioning

confidence: 99%

Tripartite genome organization of a natural type 2 vaccine/nonvaccine recombinant poliovirus

Georgescu

Delpeyroux²,

Crainic³

1995

Journal of General Virology

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Intertypic vaccine/vaccine recombinant polioviruses are frequently isolated from vaccine-associated paralytic poliomyelitis cases (VAPP). We identified a vaccine/ nonvaccine poliovirus recombinant as the causative agent of a lethal VAPP. Partial RNA sequencing revealed a tripartite recombinant structure of the viral genome. This consisted of a central capsid core of vaccine origin flanked by two units of nonvaccine origin. The first nonvaccine genomic unit spanned the whole 5' noncoding region, and the second one almost the entire nonstructural protein-coding region and the 3' noncoding region. Amino acid and nucleotide sequence similarities in the 3' and 5' unidentified regions indicated that the viral donor(s) were poliovirus species, suggesting recombination between a vaccine-derived and a wild poliovirus. The nonvaceine donor(s) could not be identified among the investigated wild polioviruses cocirculating in the same geographical area. This is the first report of a natural recombination event occurring in the 5' genomic extremity of poliovirus. The neurovirulence for transgenic mice and the pathogenicity for humans of the recombinant suggested that the modular genomic organization of this virus might have conferred a selective advantage over its vaccine parent.

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“…Natural genetic recombination in PV, another mechanism of variation in Sabin strains, was demonstrated many years ago (14,32,33) (for reviews, see references 4 and 19). Sabin vaccine PV-derived strains with recombinant intertypic genomes have been found to occur naturally (17,22) and to be selected frequently in the gut of VAPP patients (9,11,21). In some cases, vaccine/ wild (V/W) PV recombinants have been found, in which vaccine-specific segments of the Sabin virus genome have been replaced by nonvaccine sequences derived from wild PVs or, perhaps, from non-polio enteroviruses (NPEVs) (10,19,21,30).…”

mentioning

confidence: 99%

Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans

Guillot

Caro

Cuervo

et al. 2000

J Virol

182

165

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In a previous study of poliovirus vaccine-derived strains isolated from patients with vaccine-associated paralytic poliomyelitis (VAPP) (9, 11), we reported that a high proportion (over 50%) of viruses had a recombinant genome. Most were intertypic vaccine/vaccine recombinants. However, some had restriction fragment length polymorphism (RFLP) profiles different from those of poliovirus vaccine strains. We demonstrate here that five such recombinants, of 88 VAPP strains examined, carried sequences of wild (nonvaccine) origin. To identify the parental wild donor of these sequences, we used RFLP profiles and nucleotide sequencing to look for similarity in the 3D polymerase-coding region of 61 wild, cocirculating poliovirus isolates (43 type 1, 16 type 2, and 2 type 3 isolates). In only one case was the donor identified, and it was a wild type 1 poliovirus. For the other four vaccine/wild recombinants, the wild parent could not be identified. The possibility that the wild sequences were of a non-poliovirus-enterovirus origin could not be excluded. Another vaccine/wild recombinant, isolated in Belarus from a VAPP case, indicated that the poliovirus vaccine/wild recombination is not an isolated phenomenon. We also found wild polioviruses (2 of 15) carrying vaccine-derived sequences in the 3 moiety of their genome. All these results suggest that genetic exchanges with wild poliovirus and perhaps with nonpoliovirus enteroviruses, are also a natural means of evolution for poliovirus vaccine strains.

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Reversion of the attenuated and temperature-sensitive phenotypes of the sabin type 3 strain of poliovirus in vaccinees

Cited by 121 publications

References 15 publications

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

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

Tripartite genome organization of a natural type 2 vaccine/nonvaccine recombinant poliovirus

Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans

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