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Using bioinformatic protein sequence similarity to investigate if SARS CoV-2 infection could cause an ocular autoimmune inflammatory reactions?
Experimental Eye Research ( IF 3.0 ) Pub Date : 2021-01-02 , DOI: 10.1016/j.exer.2020.108433
Işıl Kutlutürk Karagöz , Marion R. Munk , Mücahit Kaya , René Rückert , Mustafa Yıldırım , Levent Karabaş

Although severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection have emerged globally, findings related to ocular involvement and reported cases are quite limited. Immune reactions against viral infections are closely related to viral and host proteins sequence similarity. Molecular Mimicry has been described for many different viruses; sequence similarities of viral and human tissue proteins may trigger autoimmune reactions after viral infections due to similarities between viral and human structures. With this study, we aimed to investigate the protein sequence similarity of SARS CoV-2 with retinal proteins and retinal pigment epithelium (RPE) surface proteins. Retinal proteins involved in autoimmune retinopathy and retinal pigment epithelium surface transport proteins were analyzed in order to infer their structural similarity to surface glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), envelope protein (E), ORF1ab polyprotein (orf1ab) proteins of SARS CoV-2. Protein similarity comparisons, 3D protein structure prediction, T cell epitopes-MHC binding prediction, B cell epitopes-MHC binding prediction and the evaluation of the antigenicity of peptides assessments were performed. The protein sequence analysis was made using the Pairwise Sequence Alignment and the LALIGN program. 3D protein structure estimates were made using Swiss Model with default settings and analyzed with TM-align web server. T-cell epitope identification was performed using the Immune Epitope Database and Analysis (IEDB) resource Tepitool. B cell epitopes based on sequence characteristics of the antigen was performed using amino acid scales and HMMs with the BepiPred 2.0 web server. The predicted peptides/epitopes in terms of antigenicity were examined using the default settings with the VaxiJen v2.0 server. Analyses showed that, there is a meaningful similarities between 6 retinal pigment epithelium surface transport proteins (MRP-4, MRP-5, RFC1, SNAT7, TAUT and MATE) and the SARS CoV-2 E protein. Immunoreactive epitopic sites of these proteins which are similar to protein E epitope can create an immune stimulation on T cytotoxic and T helper cells and 6 of these 9 epitopic sites are also vaxiJen. These result imply that autoimmune cross-reaction is likely between the studied RPE proteins and SARS CoV-2 E protein. The structure of SARS CoV-2, its proteins and immunologic reactions against these proteins remain largely unknown. Understanding the structure of SARS CoV-2 proteins and demonstration of similarity with human proteins are crucial to predict an autoimmune response associated with immunity against host proteins and its clinical manifestations as well as possible adverse effects of vaccination.



中文翻译:

使用生物信息学蛋白质序列相似性研究SARS CoV-2感染是否会引起眼部自身免疫性炎症反应?

尽管全球已出现严重的急性呼吸系统综合症冠状病毒2(SARS CoV-2)感染,但与眼部受累和报告病例有关的发现非常有限。针对病毒感染的免疫反应与病毒和宿主蛋白序列的相似性密切相关。分子拟态已被描述用于许多不同的病毒。由于病毒和人体结构之间的相似性,病毒和人体组织蛋白的序列相似性可能会在病毒感染后触发自身免疫反应。通过这项研究,我们旨在研究SARS CoV-2与视网膜蛋白和视网膜色素上皮(RPE)表面蛋白的蛋白序列相似性。为了推断它们与表面糖蛋白(S),核衣壳磷蛋白(N),膜糖蛋白(M),包膜蛋白(E),ORF1ab多聚蛋白( orf1ab)SARS CoV-2蛋白。进行蛋白质相似性比较,3D蛋白质结构预测,T细胞表位-MHC结合预测,B细胞表位-MHC结合预测以及肽的抗原性评估。使用成对序列比对和LALIGN程序进行蛋白质序列分析。使用默认设置的Swiss Model进行3D蛋白质结构估算,并使用TM-align Web服务器进行分析。使用免疫表位数据库和分析(IEDB)资源Tepitool进行T细胞表位鉴定。基于氨基酸序列特征的B细胞表位是通过BepiPred 2.0 Web服务器使用氨基酸标度和HMM进行的。使用VaxiJen v2.0服务器的默认设置,检查了根据抗原性预测的肽/表位。分析表明,在6种视网膜色素上皮表面转运蛋白(MRP-4,MRP-5,RFC1,SNAT7,TAUT和MATE)与SARS CoV-2 E蛋白之间存在有意义的相似性。这些蛋白质的免疫反应性抗原决定簇位点类似于蛋白质E表位,可对T细胞毒性和T辅助细胞产生免疫刺激,这9个抗原决定簇位点中的6个也被激活。这些结果暗示所研究的RPE蛋白和SARS CoV-2 E蛋白之间可能存在自身免疫交叉反应。SARS CoV-2的结构,其蛋白质以及针对这些蛋白质的免疫反应仍然未知。了解SARS CoV-2蛋白的结构并证明与人蛋白的相似性对于预测与针对宿主蛋白的免疫力及其临床表现以及疫苗接种可能产生的不良反应相关的自身免疫反应至关重要。

更新日期:2021-01-07
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