A Meta-Analysis of the Existing Knowledge of Immunoreactivity against Hepatitis C Virus (HCV)
A Meta-Analysis of the Existing Knowledge of Immunoreactivity against Hepatitis C Virus (HCV)
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DOI：
10.1371/journal.pone.0038028
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发表时间：
2012-05-31
期刊：
影响因子：
3.7
通讯作者：
Sette, Alessandro
中科院分区：
文献类型：
--
作者：
Kim, Yohan;Vaughan, Kerrie;Sette, Alessandro
大约3%的世界人口感染了丙型肝炎病毒，这是一个重大的全球卫生挑战。近400份不同的科学报告提供了与来自丙型肝炎病毒文献的T细胞和抗体表位相关的免疫学数据。对免疫表位数据库(IEDB)中所有与丙型肝炎病毒相关的表位进行分析，分别揭示了1500多个不同的T细胞表位和1900个不同的抗体表位。所有数据的清单揭示了从宿主和产生序列的丙型肝炎病毒基因类型方面的具体趋势。进一步的分析发现，这些大量的表位反映了重叠的结构，以及来自不同丙型肝炎病毒分离株的同源序列。为了获取和可视化这些信息，我们开发了一种新的策略，将大量表位数据组合在一起，将它们映射到参考基因组上，并显示阳性反应的频率。汇编了数百项不同研究的丙型肝炎病毒免疫反应性，揭示了迄今为止丙型肝炎病毒免疫表位数据的复杂和全面的图景。研究结果指出了每种丙型肝炎病毒蛋白在抗体、CD4和CD8反应水平上更强烈的反应或研究活动的区域。总的来说，不同效应器免疫功能的靶区是不同的，抗体反应性与亲水性正相关，而T细胞反应性与疏水性相关。在序列水平上，T细胞和B细胞经常识别的表位与低变异性相关，因此我们的分析突出了潜在的实际应用兴趣领域。进一步分析了人类的反应性，以确定与急性和慢性感染相关的反应性差异模式，揭示糖基化对T细胞的明显影响，但不影响抗体反应，并强调涉及与病毒中和相关的抗体表位的研究较少。
Approximately 3% of the world population is infected by HCV, which represents a major global health challenge. Almost 400 different scientific reports present immunological data related to T cell and antibody epitopes derived from HCV literature. Analysis of all HCV-related epitope hosted in the Immune Epitope Database (IEDB), a repository of freely accessible immune epitope data, revealed more than 1500 and 1900 distinct T cell and antibody epitopes, respectively. The inventory of all data revealed specific trends in terms of the host and the HCV genotypes from which sequences were derived. Upon further analysis we found that this large number of epitopes reflects overlapping structures, and homologous sequences derived from different HCV isolates. To access and visualize this information we developed a novel strategy that assembles large sets of epitope data, maps them onto reference genomes and displays the frequency of positive responses. Compilation of the HCV immune reactivity from hundreds of different studies, revealed a complex and thorough picture of HCV immune epitope data to date. The results pinpoint areas of more intense reactivity or research activities at the level of antibody, CD4 and CD8 responses for each of the individual HCV proteins. In general, the areas targeted by the different effector immune functions were distinct and antibody reactivity was positively correlated with hydrophilicity, while T cell reactivity correlated with hydrophobicity. At the sequence level, epitopes frequently recognized by both T cell and B cell correlated with low variability, and our analysis thus highlighted areas of potential interest for practical applications. The human reactivity was further analyzed to pinpoint differential patterns of reactivity associated with acute versus chronic infection, to reveal the apparent impact of glycosylation on T cell, but not antibody responses, and to highlight a paucity of studies involved antibody epitopes associated with virus neutralization.