Characterization of susceptibility variants of poliovirus grown in the presence of favipiravir
Characterization of susceptibility variants of poliovirus grown in the presence of favipiravir
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DOI：
10.1016/j.jmii.2017.03.004
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发表时间：
2018-10-01
影响因子：
7.4
通讯作者：
Shiraki, Kimiyasu
中科院分区：
文献类型：
--
作者：
Daikoku, Tohru;Mizuguchi, Mineyuki;Shiraki, Kimiyasu
背景资料：T-705（法匹拉韦）是流感病毒RNA依赖性RNA聚合酶的强效抑制剂，尚未分离出法匹拉韦耐药病毒。脊髓灰质炎病毒RNA聚合酶已得到很好的表征，并在脊髓灰质炎病毒中检测了耐药病毒的分离。在存在法匹拉韦的情况下，在传代过程中分离Sabin株，并对其易感性和RNA聚合酶序列进行表征。5种变体（其对亲本脊髓灰质炎病毒空斑形成的50%抑制浓度为0.47-1.88倍）在RNA聚合酶的3D基因中具有氨基酸变异。结论：法匹拉韦作为链终止剂，不会像利巴韦林那样作为诱变剂掺入和复制而引起致死性突变，未分离到耐药突变株。高复制水平将产生突变，导致法匹拉韦耐药性，因为产生了利巴韦林耐药性，但产生的突变对RNA聚合酶功能是致命的。Copyright（C）2017，Taiwan Society of Microbiology.出版社：Elsevier Taiwan LLC这是CC BY-NC-ND许可下的开放获取文章。
Background: T-705 (favipiravir) is a potent inhibitor of RNA-dependent RNA polymerases of influenza viruses and no favipiravir-resistant virus has been isolated. Poliovirus RNA polymerase has been well characterized and isolation of resistant virus was examined in poliovirus.Methods: Susceptibility variants of poliovirus I (Sabin strain) were isolated during passages in the presence of favipiravir and characterized for their susceptibility and the sequence of RNA polymerase.Results: Five variants with 0.47-1.88 times the 50% inhibitory concentration for plaque formation of the parent poliovirus had amino acid variations in the 3D gene of the RNA polymerase. The distribution of amino acid variations was not related to ribavirin resistance, and two amino acid variation sites were found near the finger domain.Conclusion: Favipiravir as a chain terminator would not be incorporated and replicate to cause lethal mutagenesis as a mutagen like ribavirin, and resistant mutants were not isolated. A high replication level would generate mutations leading to favipiravir resistance as ribavirin resistance was generated, but generated mutations would be lethal to the RNA polymerase function. Copyright (C) 2017, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license.