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

Epitope-based universal vaccine for Human T-lymphotropic virus-1 (HTLV-1).
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DOI:
10.1371/journal.pone.0248001
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Shahik SM
Shahik SM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Raza MT;Mizan S;Yasmin F;Akash AS;Shahik SM

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人类T细胞白血病病毒1型(HTLV-1)是在人类体内发现的第一种致癌性人类逆转录病毒,全球至少有1000-1500万人感染。日本南部、加勒比海地区、中美洲和南美洲、中东、美拉尼西亚和非洲赤道地区存在大面积的HTLV-1流行区。HTLV-1Tax病毒蛋白被认为在HTLV-1相关疾病中发挥关键作用。我们已经使用了大量的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。HTLV-1 Tax病毒蛋白的构象线性B细胞和T细胞表位已被预测为可能作为疫苗候选的集体使用。在电子计算机研究的基础上,发现了两个B细胞表位KEADDNDHEPQISPGGLEPSEKHFR和DGTPMISGPCPKDGQPS,它们的跨度分别为324-349和252-268,而T细胞表位LLFGYPVYV、ITWPLLPHV和GLLPFHSTL的跨度分别为11-19、163-171和233-241。在这些表位的不同组合产生的不同疫苗结构中,我们预测的疫苗结构被发现是最具抗原性的,得分为0.57。T细胞表位与人类白细胞抗原A*0201有很强的相互作用,提示这些表位能引起显著的免疫反应。分子对接研究还表明,TLR4疫苗构建体具有很高的结合亲和力。该研究是在进行三维蛋白质建模的同时,对Tax蛋白的抗原决定簇进行预测。这项研究揭示了一种潜在的多表位疫苗,它可以提高对HTLV-1的预期免疫应答,并有助于开发有效的抗人T淋巴细胞病毒疫苗。
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.
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发表时间: 1993-09-01
期刊: PROTEIN SCIENCE
影响因子: 8
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发表时间: 2008-08-14
期刊: Retrovirology
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