Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Department of Laboratory Medicine, E-Da Hospital, Kaohsiung 824, Taiwan.
Viruses. 2022 Feb 10;14(2):364. doi: 10.3390/v14020364.
genus has over one hundred genotypes and could cause several kinds of severe animal and human diseases. Understanding the role of conserved residues in the VP1 capsid protein among the genus may lead to anti-enteroviral drug development. The highly conserved residues were found to be located at the loop and ß-barrel intersections. To elucidate the role of these VP1 residues among the genus, alanine substitution reverse genetics (rg) variants were generated, and virus properties were investigated for their impact. Six highly conserved residues were identified as located near the inside of the canyon, and four of them were close to the ß-barrel and loop intersection. The variants rgVP1-R86A, rgVP1-P193A, rgVP1-G231A, and rgVP1-K256A were unable to be obtained, which may be due to disruption in the virus replication process. In contrast, rgVP1-E134A and rgVP1-P157A replicated well and rgVP1-P157A showed smaller plaque size, lower viral growth kinetics, and thermal instability at 39.5°C when compared to the rg wild type virus. These findings showed that the conserved residues located at the ß-barrel and loop junction play roles in modulating viral replication, which may provide a pivotal role for pan-enteroviral inhibitor candidate.
该属有超过一百种基因型，可能导致多种严重的动物和人类疾病。了解该属中 VP1 衣壳蛋白保守残基的作用可能导致抗肠病毒药物的开发。高度保守的残基被发现位于环和β-桶交界处。为了阐明这些 VP1 残基在该属中的作用，生成了丙氨酸取代反向遗传（rg）变体，并研究了它们对病毒特性的影响。确定了六个高度保守的残基位于峡谷内部附近，其中四个残基靠近β-桶和环的交界处。无法获得 rgVP1-R86A、rgVP1-P193A、rgVP1-G231A 和 rgVP1-K256A 变体，这可能是由于病毒复制过程的破坏。相比之下，rgVP1-E134A 和 rgVP1-P157A 复制良好，rgVP1-P157A 与 rg 野生型病毒相比，噬菌斑更小，病毒生长动力学更低，在 39.5°C 时热稳定性更低。这些发现表明，位于β-桶和环交界处的保守残基在调节病毒复制中起作用，这可能为泛肠病毒抑制剂候选物提供关键作用。
