Evolution of Type 2 Vaccine Derived Poliovirus Lineages. Evidence for Codon-Specific Positive Selection at Three Distinct Locations on Capsid Wall

Tapani Hovi,Carita Savolainen-Kopra,Soile Blomqvist,Teemu Smura,Haider Al-Hello,Merja Roivainen,Dhanasekaran Vijaykrishna

doi:10.1371/journal.pone.0066836

Tapani Hovi, Carita Savolainen-Kopra + Show 5 more

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https://doi.org/10.1371/journal.pone.0066836

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Journal: PLoS ONE	Publication Date: Jun 28, 2013
Citations: 42	License type: CC BY 4.0

Affiliation: Finnish Institute for Health and Welfare

Abstract

Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003–2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2) were compared to those of type 1 and type 3 wild poliovirus (WPV) lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin) by 12.5–15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv) bias and strikingly lower Ts/Tv rate ratios at the 2nd codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2nd codon position was also found in the large set of VP1 sequences of Nigerian circulating (c)VDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance.

Highlights

Polioviruses (Species Human enterovirus C, genus Enterovirus, family Picornaviridae) are considered to be among the most rapidly evolving viruses with an estimated overall nucleotide substitution rate of about 0.01 substitutions per site per year in the capsid coding region [1,2,3,4,5,6,7,8,9,10]
Common path of evolution and designated lineages of Slovakian VDPV strains As reported in the adjacent article [29], the 110 environmental type 2 poliovirus strains isolated in Slovakia in 2003–2005 were monophyletic and showed closest relationship to the PV2 Sabin strain in all genomic regions, widely divergent in the capsid protein coding sequences, and designated as VDPVs
To study the assumed initially common evolutionary pathway of the SVK-aVDPV2 strains we searched for conserved nucleotide substitutions compared to the sequence of PV2 Sabin

Summary

Introduction

Polioviruses (Species Human enterovirus C, genus Enterovirus, family Picornaviridae) are considered to be among the most rapidly evolving viruses with an estimated overall nucleotide substitution rate of about 0.01 substitutions per site per year in the capsid coding region [1,2,3,4,5,6,7,8,9,10]. In the pre-vaccine era, cumulative poliovirus diversification had resulted, within each serotype, in several co-circulating wild-type poliovirus clades, the designated genotypes [16] While both deletions and recombinations may occur in the capsid protein coding part of poliovirus genome [17,18,19,20] these changes rather rarely persist in WPV lineages, as compared to recombinations occurring in the untranslated and non-structural protein coding parts of the genome. While the overall accumulation of mutations in the capsid coding region of replicating polioviruses is considered to follow first order molecular clock kinetics, it is known that in the longer run, saturation of nucleotide substitutions will become evident. As regards the timing of onset of the saturation, different types of substitutions, i.e. synonymous vs. non-synonymous or transitions vs. transversions, differ remarkably [6]

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