The Temperature Sensitivity of the Sabin Type 3 Vaccine Strain of Poliovirus: Molecular and Structural Effects of a Mutation in the Capsid Protein VP3

Minor, Philip D.; Dunn, Glynis; Evans, D. M. A.; Magrath, D. I.; John, A.; Howlett, J.; Phillips, A.C.; Westrop, Gareth D.; Wareham, K A; Almond, Jeffrey W.; Hogle, James M.

doi:10.1099/0022-1317-70-5-1117

Cited by 79 publications

(50 citation statements)

References 8 publications

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“…The replacements, which were found relatively often in this study but were not obviously related to antigenicity, appeared to belong only to the class of deattenuating fitness-increasing alterations, as previously reported for mutations at position 1143 in type 2 (36,49) and positions 1054 and 3091 in type 3 (15,34,43,65). The latter appeared to increase the efficiency of virion maturation (35).…”

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confidence: 53%

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Antigenic Evolution of Vaccine-Derived Polioviruses: Changes in Individual Epitopes and Relative Stability of the Overall Immunological Properties

Yakovenko

Cherkasova

Rezapkin

et al. 2006

J Virol

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The Sabin oral poliovirus vaccine (OPV) readily undergoes changes in antigenic sites upon replication in humans. Here, a set of antigenically altered descendants of the three OPV serotypes (76 isolates) was characterized to determine the driving forces behind these changes and their biological implications. The amino acid residues of OPV derivatives that lie within or close to the known antigenic sites exhibited a marked tendency to be replaced by residues characteristic of homotypic wild polioviruses, and these changes may occur very early in OPV evolution. The specific amino acid alterations nicely correlated with serotype-specific changes in the reactivity of certain individual antigenic sites, as revealed by the recently devised monoclonal antibody-based enzyme-linked immunosorbent assay. In comparison to the original vaccine, small changes, if any, in the neutralizing capacity of human or rabbit sera were observed in highly diverged vaccine polioviruses of three serotypes, in spite of strong alterations of certain epitopes. We propose that the common antigenic alterations in evolving OPV strains largely reflect attempts to eliminate fitness-decreasing mutations acquired either during the original selection of the vaccine or already present in the parental strains. Variability of individual epitopes does not appear to be primarily caused by, or lead to, a significant immune evasion, enhancing only slightly, if at all, the capacity of OPV derivatives to overcome immunity in human populations. This study reveals some important patterns of poliovirus evolution and has obvious implications for the rational design of live viral vaccines.

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confidence: 53%

“…Among them, mutations known to be involved in restoring neurovirulence or eliminating the temperature-sensitive phenotype of vaccine derivatives (34,36,43,49,65) were relatively frequently observed, in particular Ile11433Thr, Val, Asn, or Ser in type 2 ( Fig. 2B) as well as Phe30913Ser and/or Ala10543Thr or Val in type 3 polioviruses (Fig.…”

Section: Resultsmentioning

confidence: 99%

Antigenic Evolution of Vaccine-Derived Polioviruses: Changes in Individual Epitopes and Relative Stability of the Overall Immunological Properties

Yakovenko

Cherkasova

Rezapkin

et al. 2006

J Virol

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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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“…Early studies with temperaturesensitive and nontemperature-sensitive variants of the Sabin vaccine strain of type 3 poliovirus pointed to 3 specific areas of the mature virus structure that appear to play a critical role in determining the stability of the virion and of assembly intermediates (Filman et al, 1989;Minor et al, 1989;Macadam et al, 1991). These sites include: (1) a pocket in the 0-barrel core of VPl, (2) the interface between 5-fold related protomers, and (3) the network formed by the N-terminal extensions of the capsid proteins in the inner surface of the virion.…”

Section: Role Of Vpo Cleavage In Virion Stabilitymentioning

confidence: 99%

Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: Structure of the empty capsid assembly intermediate at 2.9 Å resolution

et al. 1994

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The crystal structure of the Pl/Mahoney poliovirus empty capsid has been determined at 2.9 A resolution. The empty capsids differ from mature virions in that they lack the viral RNA and have yet to undergo a stabilizing maturation cleavage of VPO to yield the mature capsid proteins VP4 and VP2. The outer surface and the bulk of the protein shell are very similar to those of the mature virion. The major differences between the 2 structures are focused in a network formed by the N-terminal extensions of the capsid proteins on the inner surface of the shell. In the empty capsids, the entire N-terminal extension of V P l , as well as portions corresponding to VP4 and the N-terminal extension of VP2, are disordered, and many stabilizing interactions that are present in the mature virion are missing. In the empty capsid, the VPO scissile bond is located some 20 A away from the positions in the mature virion of the termini generated by VPO cleavage. The scissile bond is located on the rim of a trefoilshaped depression in the inner surface of the shell that is highly reminiscent of an RNA binding site in bean pod mottle virus. The structure suggests plausible (and ultimately testable) models for the initiation of encapsidation, for the RNA-dependent autocatalytic cleavage of VPO, and for the role of the cleavage in establishing the ordered N-terminal network and in generating stable virions.Keywords: capsid proteins; empty capsid; encapsidation initiation; maturation cleavage; poliovirus; viral RNA; virion stability Poliovirus is a member of the picornavirus family. This family includes a large number of related small spherical viruses consisting entirely of a protein shell (approximately 300 A in diameter) and a single-stranded RNA genome (-7,500 nucleotides) of positive polarity. The family is subdivided into several genera, including the enteroviruses (polioviruses, coxsackieviruses,

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The Temperature Sensitivity of the Sabin Type 3 Vaccine Strain of Poliovirus: Molecular and Structural Effects of a Mutation in the Capsid Protein VP3

Cited by 79 publications

References 8 publications

Antigenic Evolution of Vaccine-Derived Polioviruses: Changes in Individual Epitopes and Relative Stability of the Overall Immunological Properties

Antigenic Evolution of Vaccine-Derived Polioviruses: Changes in Individual Epitopes and Relative Stability of the Overall Immunological Properties

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

Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: Structure of the empty capsid assembly intermediate at 2.9 Å resolution

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