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

机译：2型疫苗衍生脊髓灰质炎病毒谱系的演变。衣壳壁上三个不同位置的特定密码子正选择的证据

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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.
机译：对2003年至2005年从斯洛伐克的污水中分离出的110种2型脊髓灰质炎病毒株的部分序列进行了详细的基因分析，这些序列很可能源自单剂口服脊髓灰质炎病毒疫苗。将这些疫苗衍生的脊髓灰质炎病毒株（SVK-aVDPV2）的进化模式分别与被认为具有单一种子株起源的1型和3型野生脊髓灰质炎病毒（WPV）谱系进行了比较。 102条独特的SVK-aVDPV VP1序列与最可能的2型/脊髓灰质炎双亲脊髓灰质炎病毒（Sabin PV2）的单系统差异为12.5–15.6％。从这种差异以及在22个月的观察期内同义异位词的累积速度来看，口服脊髓灰质炎病毒疫苗的相关剂量已于12年前施用于未知的接受者。观察期内核苷酸取代的模式与WPV1或3的研究谱系不同，包括较低的过渡/转化（Ts / Tv）偏倚和在第2次嘌呤和嘧啶的密码子位置。在尼日利亚循环（c）VDPV2的VP1序列的大集合中，以及在西班牙裔cVDPV1和埃及的较小的VP1序列中，也发现了在2 密码子位置的过渡相对较低的偏好在芬兰最近从污水中分离出的cVDPV2暴发以及aVDPV1和aVDPV2菌株中。 VP1序列中同义与非同义替代率的密码子分析表明，在五个密码子中，编码位点24、144、147、221和222处的氨基酸的密码子在观察期内可能是阳性选择。我们得出结论，在长期感染中脊髓灰质炎病毒VP1进化的模式可能与WPV流行中发现的模式不同。需要对足够大的独立数据集进行进一步研究，以确认该建议并揭示其潜在意义。

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