Hadj Hassine Ikbel, Gharbi Jawhar, Amara Imene, Alyami Ameera, Subei Reem, Almalki Mohammed, Hober Didier, M'hadheb Manel Ben
Virology and Antiviral Strategies Research Unit, Institute of Biotechnology, University of Monastir, BP74, Monastir 5000, Tunisia.
Department of Biological Sciences, College of Science, King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia.
Microorganisms. 2023 May 1;11(5):1192. doi: 10.3390/microorganisms11051192.
The aim of the present study was, first, to clone the VP1 gene of the human coxsackievirus B4 strain E2 (CVB4E2) in the prokaryotic pUC19 plasmid expression vector then to compare it with the structural capsid proteins of the same strain using bioinformatic tools. PCR colony amplification followed through a restriction digestion analysis and sequencing process which affirmed the success of the cloning process. SDS-PAGE and Western Blotting were used to characterize the purified recombinant viral protein expressed in bacteria cells. The BLASTN tool revealed that the nucleotide sequence of the recombinant VP1 (rVP1) expressed by pUC19 highly matched the target nucleotide sequence of the diabetogenic CVB4E2 strain. Secondary structure and three-dimension structure prediction suggested that rVP1, such as wild-type VP1, is chiefly composed of random coils and a high percentage of exposed amino acids. Linear B-cell epitope prediction showed that several antigenic epitopes are likely present in rVP1 and CVB4E2 VP1 capsid protein. Additionally, phosphorylation site prediction revealed that both proteins may affect the signal transduction of host cells and can be involved in virus virulence. The present work highlights the usefulness of cloning and bioinformatics characterizations for gene investigation. Furthermore, the collected data are helpful for future experimental research related to the development of immunodiagnostic reagents and subunit vaccines based on the expression of immunogenic viral capsid proteins.
本研究的目的,首先是在原核pUC19质粒表达载体中克隆人柯萨奇病毒B4 E2株(CVB4E2)的VP1基因,然后使用生物信息学工具将其与同一毒株的结构衣壳蛋白进行比较。通过限制性消化分析和测序过程进行PCR菌落扩增,证实了克隆过程的成功。使用SDS-PAGE和蛋白质免疫印迹法对在细菌细胞中表达的纯化重组病毒蛋白进行表征。BLASTN工具显示,由pUC19表达的重组VP1(rVP1)的核苷酸序列与致糖尿病CVB4E2株的目标核苷酸序列高度匹配。二级结构和三维结构预测表明,rVP1与野生型VP1一样,主要由无规卷曲和高比例的暴露氨基酸组成。线性B细胞表位预测表明,rVP1和CVB4E2 VP1衣壳蛋白中可能存在几个抗原表位。此外,磷酸化位点预测表明,这两种蛋白可能影响宿主细胞的信号转导,并可能参与病毒毒力。本研究突出了克隆和生物信息学表征在基因研究中的有用性。此外,所收集的数据有助于未来基于免疫原性病毒衣壳蛋白表达开发免疫诊断试剂和亚单位疫苗的实验研究。