Viruses selectively mutate their CD8+ T-cell epitopes--a large-scale immunomic analysis.
Viruses selectively mutate their CD8+ T-cell epitopes--a large-scale immunomic analysis.
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DOI：
10.1093/bioinformatics/btp221
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Louzoun Y
中科院分区：
文献类型：
--
作者：
Vider-Shalit T;Sarid R;Maman K;Tsaban L;Levi R;Louzoun Y
动机：病毒利用各种手段逃避免疫检测。一种常见的逃避策略是去除CD8+细胞毒性t淋巴细胞表位。我们在此使用多种生物信息学工具和大量基因组数据的组合来计算超过1300种病毒在许多HLA等位基因中呈现的表位库。我们定义了“免疫库大小得分”，它代表了蛋白质内的表位密度与预期密度之间的比率。这个分数用于研究病毒免疫逃避。结果：我们发现病毒蛋白通常比人蛋白具有更高的表位密度。这种差异是由于人类MHC分子与病毒的典型氨基酸使用非常吻合。在不同的病毒中，感染人类的病毒比非人类病毒呈现更少的表位。这种选择不是在氨基酸使用水平上，而是通过去除特定的表位。在单个病毒中，并非所有蛋白质都表达相同的表位密度。在病毒生命周期早期表达的蛋白比晚期表达的蛋白具有更低的表位密度。在非人类病毒中没有观察到这种差异。早期抗原表位的移除和对晚期病毒蛋白的细胞免疫反应的靶向，使病毒在其宿主细胞被T细胞破坏之前有一段时间的繁殖间隔。联系:louzouy@math.biu.ac.il
Motivation: Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CD8+cytotoxic T-lymphocyte epitopes. We here use a combination of multiple bioinformatic tools and large amount of genomic data to compute the epitope repertoire presented by over 1300 viruses in many HLA alleles. We define the ‘Size of Immune Repertoire score’, which represents the ratio between the epitope density within a protein and the expected density. This score is used to study viral immune evasion. Results: We show that viral proteins in general have a higher epitope density than human proteins. This difference is due to a good fit of the human MHC molecules to the typical amino-acid usage of viruses. Among different viruses, viruses infecting humans present less epitopes than non-human viruses. This selection is not at the amino-acid usage level, but through the removal of specific epitopes. Within a single virus, not all proteins express the same epitopes density. Proteins expressed early in the viral life cycle have a lower epitope density than late proteins. Such a difference is not observed in non-human viruses. The removal of early epitopes and the targeting of the cellular immune response to late viral proteins, allow the virus a time interval to propagate before its host cells are destroyed by T cells. Contact: louzouy@math.biu.ac.il
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影响因子：
56.9
作者：
COFFIN, JM
通讯作者：
COFFIN, JM
影响因子：
14.9
作者：
Robinson, J;Waller, MJ;Marsh, SGE
通讯作者：
Marsh, SGE
影响因子：
5.4
作者：
Almani M;Raffaeli S;Vider-Shalit T;Tsaban L;Fishbain V;Louzoun Y
通讯作者：
Louzoun Y
从CD8+ T细胞免疫中逃脱的突变：HCV的进化，从黑猩猩到人。
影响因子：
15.3
作者：
Bowen, David G;Walker, Christopher M
通讯作者：
Walker, Christopher M
DOI：
10.1021/ci030461e
发表时间：
2003-07-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
McSparron, H;Blythe, MJ;Flower, DR
通讯作者：
Flower, DR