Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumtani 12120, Thailand.
Thammasat University Research Unit in Molecular Pathogenesis and Immunology of Infectious Diseases, Thammasat University, Pathumthani 12120, Thailand.
Int J Mol Sci. 2023 Jun 7;24(12):9865. doi: 10.3390/ijms24129865.
Enterovirus A71 (EV-A71) is one of the causative agents of hand-foot-mouth disease, which can be associated with neurocomplications of the central nervous system. A limited understanding of the virus's biology and pathogenesis has led to the unavailability of effective anti-viral treatments. The EV-A71 RNA genome carries type I internal ribosomal entry site (IRES) at 5' UTR that plays an essential role in the viral genomic translation. However, the detailed mechanism of IRES-mediated translation has not been elucidated. In this study, sequence analysis revealed that the domains IV, V, and VI of EV-A71 IRES contained the structurally conserved regions. The selected region was transcribed in vitro and labeled with biotin to use as an antigen for selecting the single-chain variable fragment (scFv) antibody from the naïve phage display library. The so-obtained scFv, namely, scFv #16-3, binds specifically to EV-A71 IRES. The molecular docking showed that the interaction between scFv #16-3 and EV-A71 IRES was mediated by the preferences of amino acid residues, including serine, tyrosine, glycine, lysine, and arginine on the antigen-binding sites contacted the nucleotides on the IRES domains IV and V. The so-produced scFv has the potential to develop as a structural biology tool to study the biology of the EV-A71 RNA genome.
肠道病毒 A71(EV-A71)是手足口病的病原体之一,可引起中枢神经系统神经并发症。由于对病毒生物学和发病机制的了解有限,目前还没有有效的抗病毒治疗方法。EV-A71 的 RNA 基因组在 5'UTR 携带 I 型内部核糖体进入位点(IRES),在病毒基因组翻译中发挥着重要作用。然而,IRES 介导的翻译的详细机制尚未阐明。在这项研究中,序列分析表明 EV-A71 IRES 的 IV、V 和 VI 结构域包含结构保守区。选择该区域进行体外转录并标记生物素,用作从原始噬菌体展示文库中筛选单链可变片段(scFv)抗体的抗原。获得的 scFv,即 scFv #16-3,特异性结合 EV-A71 IRES。分子对接表明 scFv #16-3 与 EV-A71 IRES 之间的相互作用是通过抗原结合位点上的氨基酸残基的偏好介导的,包括与 IRES 结构域 IV 和 V 上的核苷酸接触的丝氨酸、酪氨酸、甘氨酸、赖氨酸和精氨酸。因此产生的 scFv 有可能作为结构生物学工具来研究 EV-A71 RNA 基因组的生物学。