[1]姚若一,范嘉琦,肖 雄,等.HLA-E与oHSV2 VP5蛋白相互作用研究[J].湖北工业大学学报,2023,(5):82-87.
 YAO Ruoyi,FAN Jiaqi,XIAO Xiong,et al.Study on the Interaction Between HLAE and oHSV2 VP5 Protein[J].,2023,(5):82-87.
点击复制

HLA-E与oHSV2 VP5蛋白相互作用研究()
分享到:

《湖北工业大学学报》[ISSN:1003-4684/CN:42-1752/Z]

卷:
期数:
2023年第5期
页码:
82-87
栏目:
出版日期:
2023-10-30

文章信息/Info

Title:
Study on the Interaction Between HLAE and oHSV2 VP5 Protein
文章编号:
1003-4684(2023)05-0082-06
作者:
姚若一范嘉琦肖 雄周 芹汪 洋胡 翰刘滨磊
湖北工业大学生物工程与食品学院,湖北 武汉 430068
Author(s):
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
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
Keywords:
HLAE oncolytic herpes simplex virus type Ⅱ proteininteraction
分类号:
Q51
文献标志码:
A
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(HSVG2)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 HLA Ⅰb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 GSTpullGdown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.
Abstract:
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 type Ⅱ(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.

参考文献/References:

[1] VEINALDER,PIDELASERRAGMARTÍG,MOULIN C,etal.OncolyticmeaslesvaccinesencodingPDG1and PDGL1 checkpoint blocking antibodies to increase tumorGspecificTcellmemory[J].MolTherOncolytG ics,2022,24:43G58. [2] ZHANG W,ZENGB,HUX,etal.Oncolyticherpes simplexvirustype2caneffectivelyinhibitcolorectal 86 湖 北 工 业 大 学 学 报 2023年第5期 cancerlivermetastasisbymodulatingtheimmunestaG tusinthetumormicroenvironmentandinducingspeG cificantitumorimmunity[J].Hum GeneTher,2021, 32(3G4):815G822. [3] KAUFMAN H L,KOHLHAPPFJ,ZLOZAA.OnG colyticviruses:anewclassofimmunotherapydrugs [J].NatRevDrugDiscov,2015,14(09):642G662. [4] O'CALLAGHANCA.StructureofNonclassicalMHC I(HLAGE,HLAGF,HLAGG,andOrthologs)[M]∥ RATCLIFFE MJH.EncyclopediaofImmunobiology. Oxford;AcademicPress.2016:178G189. [5] WUZ,LIANGJ,WANGZ,etal.HLAGEexpression indiffuseglioma:relationshipwithclinicopathological featuresandpatientsurvival[J].BMC Neurol,2020, 20(01):59. [6] PALMISANO GL,CONTARDIE,MORABITO A, etal.HLAGEsurfaceexpressionisindependentofthe availabilityof HLA classIsignalsequenceGderived peptidesinhumantumorcelllines [J].HumImmuG nol,2005,66(01):1G12. [7] PETRIEEJ,CLEMENTSCS,LINJ,etal.CD94G NKG2A recognition of human leukocyte antigen (HLA)GEboundtoan HLAclassIleadersequence [J].JExpMed,2008,205(03):725G735. [8] ZHENZJ,LINGJY,CAIY,etal.ImpactofHLAG EgenepolymorphismonHLAGEexpressionintumor cellsandprognosisinpatientswithstageⅢ colorectal cancer[J].MedOncol,2013,30(01):482. [9]  VAN HALL T,ANDRÉP,HOROWITZ A,etal. Monalizumab:inhibitingthenovelimmunecheckpoint NKG2A[J].JImmunotherCancer,2019,7(01):263. [10]ANDRÉP,DENISC,SOULASC,etal.AntiGNKG2A mAbIsacheckpointinhibitorthatpromotesantiG tumorimmunitybyunleashingBoth Tand NKcells [J].Cell,2018,175(07):1731G1743. [11]ULBRECHT M,MARTINOZZIS,GRZESCHIK M, etal.Cuttingedge:thehumancytomegalovirusUL40 geneproductcontainsaligandforHLAGEandprevents NKcellGmediatedlysis [J].JImmunol,2000,164 (10):5019G5022. [12]NATTERMANNJ,NISCHALKE H D,HOFMEISG TER V,etal.TheHLAGA2restrictedTcellepitope HCVcore35G44stabilizesHLAGEexpressionandinG hibitscytolysis mediatedbynaturalkillercells [J]. AmJPathol,2005,166(02):443G453. [13]MBIRIBINDIB,PENAJK,ARVEDSON MP,etal. EpsteinGBarrviruspeptidesderivedfromlatentcycle proteinsalterNKG2A+NKcelleffectorfunction[J]. SciRep,2020,10(01):19973. [14]TRANRK,LIEUPT,AGUILARS,etal.Altering theexpressionkineticsofVP5resultsinalteredviruG lenceandpathogenesisofherpessimplexvirustype1 inmice[J].JVirol,2002,76(05):2199G2205. [15]YUAN S,WANGJL,ZHU DJ,etal.CryoGEM structureofaherpesviruscapsidat3.1Å [J].Science, 2018,360(6384):1G11.

备注/Memo

备注/Memo:
[收稿日期]2022- 02 -23 [第一作者]姚若一(1997-),女,湖北襄阳人,湖北工业大学硕士研究生,研究方向为生物工程. [通信作者]刘滨磊(1962-),男,湖北武汉人,湖北工业大学教授,研究方向为生物制药.
更新日期/Last Update: 2023-10-30