Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase.
Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase.
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DOI：
10.3390/v7102894
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发表时间：
2015-10-26
期刊：
影响因子：
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通讯作者：
Boehr DD
中科院分区：
文献类型：
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作者：
Liu X;Musser DM;Lee CA;Yang X;Arnold JJ;Cameron CE;Boehr DD
Sabin I脊髓灰质炎病毒减毒活疫苗株编码四个氨基酸变化（即，D53 N、Y73 H、K250 E和T362 I）。我们以前已经表明，T362I取代导致较低的保真度RdRp，和编码这种变体的病毒在脊髓灰质炎病毒的小鼠模型中被减毒。鉴于这些结果，令人惊讶的是，Sabin I RdRp的核苷酸掺入速率和核碱基保真度与野生型酶相似，尽管Sabin I RdRp对具有修饰的糖基的核苷酸的选择性较低。我们认为其他Sabin氨基酸的变化（即，D53 N、Y73 H、K250 E）有助于重新建立核苷酸掺入率和接近野生型水平的核苷酸区分，这可能是病毒繁殖及其作为疫苗株效力的要求。这些结果还表明，Sabin I RdRp的核碱基保真度可能不会有助于病毒减毒。
The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.