The HIV hide and seek game: an immunogenomic analysis of the HIV epitope repertoire.
The HIV hide and seek game: an immunogenomic analysis of the HIV epitope repertoire.
复制标题
HIV 捉迷藏游戏：HIV 表位库的免疫基因组分析。
DOI：
10.1097/qad.0b013e32832c492a
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Louzoun,Yoram
中科院分区：
文献类型：
--
作者：
Vider-Shalit,Tal;Almani,Michal;Sarid,Ronit;Louzoun,Yoram
背景：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（CTL）表位。方法：在这里，我们使用生物信息学工具计算了多个人类白细胞抗原等位基因中超过8000个HIV序列所呈现的HIV CTL表位库。我们定义了“免疫库大小”（SIR）评分，它代表了蛋白质中预测表位的数量与相同蛋白质的混乱版本中预期表位的数量之间的比率。结果：我们发现HIV蛋白的表位比预期的要少，并且从SIV到最近的HIV序列，表位的数量逐渐减少。HIV的SIR评分的降低伴随着表位内替换突变的高频率。不同HIV蛋白的SIR评分并不统一。在细胞感染早期表达的调控蛋白Tat和Rev具有较低的SIR评分，而较晚表达的病毒相关基因Env、Pol和Gag具有较高的SIR评分。实际上，Gag的SIR分数会随着时间的推移而增加。结论：我们假设我们的结果反映了HIV免疫逃避策略。这包括针对病毒结构和酶蛋白的CTL免疫反应，使病毒在宿主细胞被CTL破坏之前有一段时间的繁殖间隔。因此，针对HIV的有效的抗HIV CTL反应也应该针对HIV寻求隐藏免疫系统的调控基因。
Background:Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CD8+ cytotoxic T-lymphocyte (CTL) epitopes.Method:Here, we use bioinformatic tools to compute the HIV CTL epitope repertoire presented by over 8000 HIV sequences in multiple Human Leukocyte Antigen alleles. We define the ‘Size of Immune Repertoire’(SIR) score, which represents the ratio between the number of the predicted epitopes within a protein and their expected number within a scrambled version of the same protein.Results:We show that HIV proteins present less epitopes than expected and that the number of epitopes gradually decreases from SIV to recent HIV sequences. The decrease of the SIR score of HIV is accompanied by a high frequency of replacement mutations within epitopes. The SIR score of the different HIV proteins is not uniform. The regulatory proteins, Tat and Rev, expressed early during cellular infection have a low SIR score, whereas virion-associated genes that are expressed later, such as Env, Pol and Gag, have a higher SIR score. Actually, the SIR score of Gag keeps increasing over time.Conclusion:We hypothesize that our results reflect an HIV immune evasion strategy. This involves the targeting of the CTL immune response to viral structural and enzyme proteins, allowing the virus a time interval to propagate before its host cells are destroyed by CTLs. An efficient anti-HIV CTL response against HIV should thus also target the regulatory genes that HIV seeks to hide from the immune system.