Vider-Shalit Tal, Fishbain Vered, Raffaeli Shai, Louzoun Yoram
Math Department, Bar Ilan University, Ramat Gan, Israel.
J Virol. 2007 Sep;81(17):9536-45. doi: 10.1128/JVI.02636-06. Epub 2007 Jul 3.
Viruses employ various modes to evade immune detection. Two possible evasion modes are a reduction of the number of epitopes presented and the mimicry of host epitopes. The immune evasion efforts are not uniform among viral proteins. The number of epitopes in a given viral protein and the similarity of the epitopes to host peptides can be used as a measure of the viral attempts to hide this protein. Using bioinformatics tools, we here present a genomic analysis of the attempts of four human herpesviruses (herpes simplex virus type 1-human herpesvirus 1, Epstein-Barr virus-human herpesvirus 4, human cytomegalovirus-human herpesvirus 5, and Kaposi's sarcoma-associated herpesvirus-human herpesvirus 8) and one murine herpesvirus (murine herpesvirus 68) to escape from immune detection. We determined the full repertoire of CD8 T-lymphocyte epitopes presented by each viral protein and show that herpesvirus proteins present many fewer epitopes than expected. Furthermore, the epitopes that are presented are more similar to host epitopes than are random viral epitopes, minimizing the immune response. We defined a score for the size of the immune repertoire (the SIR score) based on the number of epitopes in a protein. The numbers of epitopes in proteins expressed in the latent and early phases of infection were significantly smaller than those in proteins expressed in the lytic phase in all tested viruses. The latent and immediate-early epitopes were also more similar to host epitopes than were lytic epitopes. A clear trend emerged from the analysis. In general, herpesviruses demonstrated an effort to evade immune detection. However, within a given herpesvirus, proteins expressed in phases critical to the fate of infection (e.g., early lytic and latent) evaded immune detection more than all others. The application of the SIR score to specific proteins allows us to quantify the importance of immune evasion and to detect optimal targets for immunotherapy and vaccine development.
病毒采用多种方式逃避免疫检测。两种可能的逃避方式是减少呈递的表位数量以及模仿宿主表位。病毒蛋白之间的免疫逃避作用并不一致。给定病毒蛋白中的表位数量以及这些表位与宿主肽的相似性可作为衡量病毒隐藏该蛋白的尝试程度的指标。利用生物信息学工具，我们在此展示了对四种人类疱疹病毒（单纯疱疹病毒1型——人类疱疹病毒1、爱泼斯坦-巴尔病毒——人类疱疹病毒4、人巨细胞病毒——人类疱疹病毒5以及卡波西肉瘤相关疱疹病毒——人类疱疹病毒8）和一种鼠疱疹病毒（鼠疱疹病毒68）逃避免疫检测尝试的基因组分析。我们确定了每种病毒蛋白呈递的CD8 T淋巴细胞表位的完整库，并表明疱疹病毒蛋白呈现的表位比预期少得多。此外，所呈现的表位比随机的病毒表位更类似于宿主表位，从而使免疫反应最小化。我们基于蛋白质中的表位数量定义了一个免疫库大小评分（SIR评分）。在所有测试病毒中，感染潜伏期和早期表达的蛋白质中的表位数量明显少于裂解期表达的蛋白质中的表位数量。潜伏和立即早期表位也比裂解表位更类似于宿主表位。分析中出现了一个明显的趋势。一般来说，疱疹病毒表现出逃避免疫检测的倾向。然而，在给定的疱疹病毒中，在对感染命运至关重要的阶段（如早期裂解和潜伏）表达的蛋白质比其他所有蛋白质更能逃避免疫检测。将SIR评分应用于特定蛋白质使我们能够量化免疫逃避的重要性，并检测免疫治疗和疫苗开发的最佳靶点。
