HLA-E与oHSV2 VP5蛋白相互作用研究  

Study on the Interaction Between HLAE and oHSV2 VP5 Protein

作　　者：姚若一 范嘉琦 肖雄 周芹 汪洋 胡翰 刘滨磊 YAO Ruoyi;FAN Jiaqi;XIAO Xiong;ZHOU Qin;WANG Yang;HU Han;LIU Binlei(College of Food and Biological Engin.,Hubei Univ.of Tech.,Wuhan 430068,China)

机构地区：[1]湖北工业大学生物工程与食品学院,湖北武汉430068

出　　处：《湖北工业大学学报》2023年第5期82-87,共6页Journal of Hubei University of Technology

摘　　要：溶瘤病毒代表了一类新的免疫治疗药物。它通过选择性杀伤肿瘤细胞和诱导全身性抗肿瘤免疫的双重作用机制,促进抗肿瘤反应。溶瘤Ⅱ型单纯疱疹病毒oHSV2是由单纯疱疹病毒Ⅱ型(HSV-2)基因改造而来的新型溶瘤病毒。人类白细胞抗原E(HLA-E)是一种HLAⅠb类分子,是CD94/NKG2A的强效抑制配体,它们的结合会抑制CTL细胞和NK细胞功能。多项研究已证实HLA-E会在人肿瘤细胞表面过表达,研究团队前期研究也表明oHSV2会在体外上调部分肿瘤细胞系表面HLA-E的表达。应用GST pull-down和质谱技术确定oHSV2的VP5蛋白(由UL19基因编码)为HLA-E的相互作用蛋白,并通过激光共聚焦实验进行了初步验证。它们相互作用的确定,为探究oHSV2是否干扰HLA-E和CD94/NKG2A的结合奠定研究基础。Oncolytic viruses represent a new class of immunotherapy therapeutic agents that promote anti-tumor responses through a dual mechanism of action that is dependent on selective tumor cell killing and the induction of systemic anti-tumor immunity.oHSV2 is a new type of oncolytic virus genetically modified from herpes simplex virus typeⅡ(HSV-2).Human leukocyte antigen E(HLA-E),an HLA I b molecule,is a potent inhibitory ligand for CD94/NKG2A.Binding of CD94/NKG2A and HLA-E inhibit CTL and NK cell functions.A number of studies have confirmed that HLA-E is over-expressed on the surface of human tumor cells.Our group's previous studies also showed that oHSV2 can upregulate the expression of HLA-E on the surface of some tumor cell lines in vitro.In this study,GST pull-down and mass spectrometry techniques were used to confirm that the VP5 protein(encoded by the UL19 gene)of oHSV2 interacts with HLA-E,and the preliminary verification was carried out by laser confocal experiments.The determination of their interaction lays a research foundation for exploring whether oHSV2 interferes with the binding of HLA-E and CD94/NKG2A,and further provides a theoretical basis for revealing the mechanism of oHSV2 anti-tumor effect exertion.

关 键 词：人类白细胞抗原E 溶瘤Ⅱ型单纯疱疹病毒 蛋白互作 

分 类 号：Q51[生物学—生物化学]