PDF(Pubmed)
Abstract：
Puumala orthohantavirus (PUUV) is an emerging zoonotic virus endemic to Europe and Russia that causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS). There are limited options for treatment and diagnosis of orthohantavirus infection, making the search for potential immunogenic candidates crucial. In the present work, various bioinformatics tools were employed to design conserved immunogenic peptides containing multiple epitopes of PUUV nucleocapsid protein. Eleven conserved peptides (90% conservancy) of the PUUV nucleocapsid protein were identified. Three conserved peptides containing multiple T and B cell epitopes were selected using a consensus epitope prediction algorithm. Molecular docking using the HPEP dock server demonstrated strong binding interactions between the epitopes and HLA molecules (ten alleles for each class I and II HLA). Moreover, an analysis of population coverage using the IEDB database revealed that the identified peptides have over 90% average population coverage across six continents. Molecular docking and simulation analysis reveal a stable interaction with peptide constructs of chosen immunogenic peptides and Toll-like receptor-4. These computational analyses demonstrate selected peptides\' immunogenic potential, which needs to be validated in different experimental systems.
摘要：
Puumala原位病毒（PUUV）是欧洲和俄罗斯特有的一种新兴的人畜共患病毒，可引起肾病流行病，轻度肾综合征出血热（HFRS）。目前治疗和诊断正瘤病毒感染的选择有限，使得寻找潜在的免疫原性候选者至关重要。在目前的工作中,各种生物信息学工具被用来设计包含PUUV核衣壳蛋白多个表位的保守免疫原性肽。鉴定了PUUV核衣壳蛋白的11种保守肽(90%保守性)。使用共有表位预测算法选择含有多个T和B细胞表位的三个保守肽。使用HPEP对接服务器的分子对接证明了表位和HLA分子之间的强结合相互作用(每种I类和II类HLA的10个等位基因)。此外，使用IEDB数据库对人口覆盖率进行的分析显示，所鉴定的肽在六大洲的平均人口覆盖率超过90％。分子对接和模拟分析揭示了与所选免疫原性肽和Toll样受体-4的肽构建体的稳定相互作用。这些计算分析证明了选定的肽的免疫原性潜力，这需要在不同的实验系统中进行验证。
