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基于表位的人嗜 T 淋巴细胞病毒 1(HTLV-1)通用疫苗。

Epitope-based universal vaccine for Human T-lymphotropic virus-1 (HTLV-1).

机构信息

Faculty of Biological Sciences, Department of Genetic Engineering and Biotechnology, University of Chittagong, Chattogram, Bangladesh.

Bioinformatics Division, Disease Biology and Molecular Epidemiology Research Group, Chattogram, Bangladesh.

出版信息

PLoS One. 2021 Apr 2;16(4):e0248001. doi: 10.1371/journal.pone.0248001. eCollection 2021.

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) was the first oncogenic human retrovirus identified in humans which infects at least 10-15 million people worldwide. Large HTLV-1 endemic areas exist in Southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. HTLV-1 TAX viral protein is thought to play a critical role in HTLV-1 associated diseases. We have used numerous bio-informatics and immuno-informatics implements comprising sequence and construction tools for the construction of a 3D model and epitope prediction for HTLV-1 Tax viral protein. The conformational linear B-cell and T-cell epitopes for HTLV-1 TAX viral protein have been predicted for their possible collective use as vaccine candidates. Based on in silico investigation two B cell epitopes, KEADDNDHEPQISPGGLEPPSEKHFR and DGTPMISGPCPKDGQPS spanning from 324-349 and 252-268 respectively; and T cell epitopes, LLFGYPVYV, ITWPLLPHV and GLLPFHSTL ranging from 11-19, 163-171 and 233-241 were found most antigenic and immunogenic epitopes. Among different vaccine constructs generated by different combinations of these epitopes our predicted vaccine construct was found to be most antigenic with a score of 0.57. T cell epitopes interacted strongly with HLA-A*0201 suggesting a significant immune response evoked by these epitopes. Molecular docking study also showed a high binding affinity of the vaccine construct for TLR4. The study was carried out to predict antigenic determinants of the Tax protein along with the 3D protein modeling. The study revealed a potential multi epitope vaccine that can raise the desired immune response against HTLV-1 and be useful in developing effective vaccines against Human T-lymphotropic virus.

摘要

人类 T 细胞白血病病毒 1 型(HTLV-1)是人类发现的第一种致癌性逆转录病毒,它至少感染了全球 1000 万至 1500 万人。日本南部、加勒比海地区、中美洲和南美洲、中东、美拉尼西亚以及非洲赤道地区存在着大量的 HTLV-1 流行地区。HTLV-1 TAX 病毒蛋白被认为在 HTLV-1 相关疾病中发挥关键作用。我们使用了许多生物信息学和免疫信息学工具,包括序列和构建工具,用于构建 HTLV-1 Tax 病毒蛋白的 3D 模型和表位预测。已经预测了 HTLV-1 Tax 病毒蛋白的构象线性 B 细胞和 T 细胞表位,以便将其作为可能的疫苗候选物进行联合使用。基于计算机模拟研究,我们发现了两个 B 细胞表位,KEADDNDHEPQISPGGLEPPSEKHFR 和 DGTPMISGPCPKDGQPS,分别位于 324-349 和 252-268 位;以及 T 细胞表位,LLFGYPVYV、ITWPLLPHV 和 GLLPFHSTL,分别位于 11-19、163-171 和 233-241 位,这些表位具有最强的抗原性和免疫原性。在所生成的不同疫苗构建体中,通过这些表位的不同组合,我们预测的疫苗构建体的抗原性最高,得分 0.57。T 细胞表位与 HLA-A*0201 强烈相互作用,提示这些表位可引起显著的免疫反应。分子对接研究还表明,疫苗构建体与 TLR4 具有很高的结合亲和力。这项研究旨在预测 Tax 蛋白的抗原决定簇,并进行 3D 蛋白建模。研究揭示了一种潜在的多表位疫苗,能够引起针对 HTLV-1 的所需免疫反应,并有助于开发针对人类 T 淋巴细胞病毒的有效疫苗。

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