James Stephen A, Joshua Istifanus A
Department of Biochemistry, Kaduna State University, Kaduna, Nigeria.
School of Data Sciences, Centre of Bioinformatics, Perdana University, Kuala Lumpur, Malaysia.
Bioinform Biol Insights. 2024 Nov 5;18:11779322241289936. doi: 10.1177/11779322241289936. eCollection 2024.
Diabetes mellitus (DM) is a metabolic syndrome characterized by hyperglycaemia, polydipsia, polyuria, and weight loss, among others. The pathophysiology for the disorders is complex and results in pancreatic abnormal function. Viruses have also been implicated in the metabolic syndrome. This study charted peptides to investigate and predict the autoimmune potential of shared sequences between 8 viral species proteins (which we termed 'diabetes-viruses') and the human pancreatic proteins. The structure and immunological relevance of shared sequences between viruses reported in DM onset and human pancreatic proteins were analysed. At nonapeptide mapping between human pancreatic protein and 'diabetic-viruses', reveal 1064 shared sequences distributed among 454 humans and 4288 viral protein sequences. The viral results showed herpesviruses, enterovirus (EV), human endogenous retrovirus, influenza A viruses, rotavirus, and rubivirus sequences are hosted by the human pancreatic protein. The most common shared nonapeptide was AAAAAAAAA, present in 30 human nonredundant sequences. Among the viral species, the shared sequence NSLEVLFQG occurred in 18 nonredundant EVs protein, while occurring merely in 1 human protein, whereas LGLDIEIAT occurred in 8 influenza A viruses overlapping to 1 human protein and KDELSEARE occurred in 2 rotaviruses. The prediction of the location of the shared sequences in the protein structures, showed most of the shared sequences are exposed and located either on the surface or cleft relative to the entire protein structure. Besides, the peptides in the viral protein shareome were predicted computationally for binding to MHC molecules. Here analyses showed that the entire 1064 shared sequences predicted 203 to be either HLA-A or B supertype-restricted epitopes. Fifty-one of the putative epitopes matched reported HLA ligands/T-cell epitopes majorly coming from EV B supertype representative allele restrictions. These data, shared sequences, and epitope charts provide important insight into the role of viruses on the onset of DM and its implications.
糖尿病（DM）是一种代谢综合征，其特征包括高血糖、多饮、多尿和体重减轻等。该病症的病理生理学很复杂，会导致胰腺功能异常。病毒也与代谢综合征有关。本研究绘制了肽段图谱，以研究和预测8种病毒物种蛋白（我们称之为“糖尿病病毒”）与人胰腺蛋白之间共享序列的自身免疫潜力。分析了糖尿病发病中报道的病毒与人胰腺蛋白之间共享序列的结构和免疫相关性。在人胰腺蛋白与“糖尿病病毒”的九肽图谱分析中，发现1064个共享序列分布在454个人类和4288个病毒蛋白序列中。病毒分析结果显示，人胰腺蛋白中存在疱疹病毒、肠道病毒（EV）、人类内源性逆转录病毒、甲型流感病毒、轮状病毒和风疹病毒序列。最常见的共享九肽是AAAAAAAAA，存在于30个人类非冗余序列中。在病毒物种中，共享序列NSLEVLFQG出现在18个非冗余EV蛋白中，而仅出现在1个人类蛋白中，而LGLDIEIAT出现在8个甲型流感病毒中且与1个人类蛋白重叠，KDELSEARE出现在2个轮状病毒中。对共享序列在蛋白质结构中的位置预测表明，大多数共享序列是暴露的，相对于整个蛋白质结构位于表面或裂隙处。此外，通过计算预测了病毒蛋白质共享组中的肽段与MHC分子的结合情况。此处分析表明，全部1064个共享序列中有203个被预测为HLA - A或B超型限制性表位。51个推定表位与报道的HLA配体/T细胞表位匹配，主要来自EV B超型代表性等位基因限制。这些数据、共享序列和表位图谱为病毒在糖尿病发病中的作用及其影响提供了重要见解。
