锥虫可变表面糖蛋白的表达调控、结构及免疫应答  

Expression Regulation,Structure and Immune Responses of Variant Surface Glycoproteins in Trypanosomes

作　　者：曾晴勤 李如松 李瑞 朱淳殷 王欣乐 何学东 环嘉玲 叶子雨 王莹 张璟 夏天奇 宋厚辉 郑亚东 杨永春 ZENG Qingqin;LI Rusong;LI Rui;ZHU Chunyin;WANG Xinle;HE Xuedong;HUAN Jialing;YE Ziyu;WANG Ying;ZHANG Jing;XIA Tianqi;SONG Houhui;ZHENG Yadong;YANG Yongchun(Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province,Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics&Advanced Technology,Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management,China-Australia Joint Laboratory for Animal Health Big Data Analytics,College of Animal Science and Technology&College of Veterinary Medicine of Zhejiang A&F University,Hangzhou 311300,China;Ningbo Customs Technical Center/Ningbo Key Laboratory of Port Biological and Food Safety Testing,Ningbo 315000,China;College of Animal Sciences(College of Bee Science),Fujian Agriculture and Forestry University,Fujian-Taiwan Key Laboratory of Animal Pathogen Biology,Fuzhou 350002,China;National Institute of Parasitic Diseases,Chinese Center for Disease Control and Prevention(Chinese Center for Tropical Diseases Research),NHC Key Laboratory of Parasite and Vector Biology,WHO Collaborating Centre for Tropical Diseases,National Center for International Research on Tropical Diseases,Shanghai 200025,China)

机构地区：[1]浙江农林大学动物科技学院/动物医学院/浙江省畜禽绿色生态健康养殖应用技术研究重点实验室/动物健康互联网检测技术浙江省工程研究中心/浙江省动物医学与健康管理国际科技合作基地/中澳动物健康大数据分析联合实验室,杭州311300 [2]宁波海关技术中心/宁波市口岸生物与食品安全检测重点实验室,宁波315000 [3]福建农林大学动物科学学院(蜂学学院)/福建-台湾动物病原生物学重点实验室,福州350002 [4]中国疾病预防控制中心寄生虫病预防控制所(国家热带病研究中心)国家卫生健康委员会寄生虫病原与媒介生物学重点实验室世界卫生组织热带病合作中心国家级热带病国际联合研究中心,上海200025

出　　处：《畜牧兽医学报》2024年第11期4829-4839,共11页ACTA VETERINARIA ET ZOOTECHNICA SINICA

基　　金：海关总署科研计划项目(2022HK040);宁波中盛产品检测有限公司技术开发项目(2023ZS003);浙江农林大学人才启动项目(2021LFR038);杭州西湖风景名胜区管委会科技发展计划项目(2023-001)。

摘　　要：锥虫是一类由媒介传播的血液原虫,可感染人和动物引起锥虫病,危害巨大。锥虫的体表为单一可变表面糖蛋白(variant surface glycoprotein,VSG)形成的致密“外套”,会在每个虫血症时期进行周期性更换,以逃避宿主免疫杀伤作用。锥虫基因组含有成百上千个VSG基因和假基因,而虫体可通过精确的表达调控保证在特定感染阶段只表达一种VSG。VSG具有良好的抗原性,这主要由位于其N端结构域(N-terminal domain,NTD)顶叶(top lobe)的免疫显性表位、糖基化修饰和亚结构域及其构象共同决定。VSG特异的IgM反应在清除锥虫感染中发挥重要作用,但IgG介导的免疫裂解作用则十分有限。宿主特异IgG免疫反应变得固化,只会针对每个VSG中有限的免疫显性表位,降低了与不同VSG之间的交叉反应。本文综述了VSG在表达调控、蛋白质结构、免疫原性及免疫应答等方面的最新研究进展,为深入认识锥虫致病机理、研制有效锥虫病防控手段提供理论参考。Trypanosomes are a type of blood-borne protozoa transmitted by vectors,which can infect humans and animals and cause trypanosomiasis being responsible for huge disease burdens.The surface of trypanosomes is a dense"coat"formed by a single variable surface glycoprotein(VSG),which regularly undergoes replacement at each stage of infection to evade host immune killing.The genomes of trypanosomes contain hundreds to thousands of VSG genes and pseudogenes,and parasites employ precise expression regulation mechanisms to exclusively express one type of VSG at each specific infection stage.VSGs have good antigenicity,which is mainly determined by the immunodominant epitopes,glycosylation modifications,subdomains and their conformation located in the top lobe of the N-terminal domain(NTD).VSG-specific IgM responses play an important role in trypanosome clearance,but the functions of IgG-mediated immune lysis are very limited.Host specific IgG immune responses become stereotyped,targeting only a limited set of immunodominant epitopes in each VSG,thus leading to reduction of cross reactivity with different VSGs.This article reviews the updates of VSG in expression regulation,protein structure,immunogenicity and immune responses,providing a theoretical basis for a profound understanding of the pathogenic mechanisms of trypanosomes and the development of effective prevention and control measures against trypanosomiasis.

关 键 词：锥虫 可变表面糖蛋白 表达调控 蛋白质结构 免疫应答 

分 类 号：S852.72[农业科学—基础兽医学]