Characterization of immunostimulatory components of orf virus (parapoxvirus ovis)
Characterization of immunostimulatory components of orf virus (parapoxvirus ovis)
复制标题
DOI：
10.1099/vir.0.028894-0
复制
发表时间：
2011-07-01
影响因子：
3.8
通讯作者：
Webert, Olaf
中科院分区：
文献类型：
--
作者：
Friebe, Astrid;Friederichs, Sonja;Webert, Olaf
灭活羊口疮病毒（ORFV，绵羊副痘病毒）在急性和慢性病毒感染的动物模型中诱导抗病毒活性，并对人类免疫细胞产生强烈影响。ORFV通过CD 14和可能的Toll样受体信号传导激活抗原呈递细胞（APC），并触发IFN-γ的释放，IFN-γ已被鉴定为抗病毒活性的关键介质。在描述病毒蛋白作为最可能的活性成分后，我们的目的是表征负责治疗效果的ORFV蛋白。通过使用牛痘病毒/ORFV表达文库，我们确定了几个多基因的DNA片段具有较强的免疫调节活性。这些片段共包含27个ORF。编码的蛋白质与病毒体结构和转录相关，但在其他方面无关。两种蛋白分别表达和纯化，并表现出免疫刺激活性。利用基因芯片技术分析ORFV诱导的基因表达谱和鉴定的片段。有趣的是，所有的活性片段诱导类似的基因表达模式，不同的只是在定量方面。显然，ORFV的几种蛋白质激活类似的细胞途径，调节APC以产生强烈的T辅助细胞1主导的免疫应答。这通过额外诱导免疫抑制机制来平衡，表明与单一细胞因子疗法相比的调节差异。我们的结论是，ORFV可能有潜力丰富抗病毒治疗的手段。
Inactivated orf virus (ORFV, parapoxvirus ovis) induces antiviral activity in animal models of acute and chronic viral infections and exerts strong effects on human immune cells. ORFV activates antigen presenting cells (APC) via CD14 and, probably, Toll-like receptor signalling, and triggers the release of IFN-gamma that has been identified as the key mediator of the antiviral activity. After delineating virus proteins as being the most likely active constituent, we aimed to characterize the ORFV proteins responsible for the therapeutic effect. By using a vaccinia virus/ORFV expression library we identified several multi-gene DNA fragments with strong immunomodulatory activity. Together these fragments contain 27 ORFs. The encoded proteins are related to virion structure and transcription but are otherwise unrelated. Two proteins were separately expressed and purified, and demonstrated immunostimulatory activity. Gene expression profiles induced by ORFV and the identified fragments were investigated by microarray analysis. Interestingly, all active fragments induced a similar gene-expression pattern, differing only in quantitative aspects. Obviously, several proteins of ORFV activate similar cellular pathways, modulating APC to generate a strong T-helper 1-dominated immune response. This was balanced by additional induction of immune dampening mechanisms, suggesting regulatory differences compared to single cytokine therapies. We conclude that ORFV may have the potential to enrich the armamentarium of antiviral therapies.