锥虫可变表面糖蛋白的表达调控、结构及免疫应答

doi:10.11843/j.issn.0366-6964.2024.11.005

Abstract

Abstract:

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.

Key words: trypanosome, variable surface glycoprotein, expression regulation, protein structure, immune response

CLC Number:

S852.72

Qingqin ZENG, Rusong LI, Rui LI, Chunyin ZHU, Xinle WANG, Xuedong HE, Jialing HUAN, Ziyu YE, Ying WANG, Jing ZHANG, Tianqi XIA, Houhui SONG, Yadong ZHENG, Yongchun YANG. Expression Regulation, Structure and Immune Responses of Variant Surface Glycoproteins in Trypanosomes[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(11): 4829-4839.

Figures/Tables 2

Fig. 1

Table 1

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调控水平 Regulation level	调控因素/分子 Regulatory factors/molecules	功能 Functions	参考文献 Reference
染色体水平 Chromosome level	染色体折叠结构域及其附近的染色质结构	确保单一VSG表达	[12]
	含VSG基因的小型染色体末端	参与VSG的选择性表达	[17]
	通用小环序列结合蛋白	通过影响染色质重塑调节VSG表达	[15]
	跨泡DNA聚合酶	维持染色体正常分离，确保单一VSG表达	[16]
转录水平 Transcription level	ESB特异蛋白1	参与招募ESB组成成分	[18]
	含SAP结构域的DNA结合蛋白	作用于表达位点启动子，抑制多种VSG表达	[19]
	卡哈尔体	参与VSG的转录、剪切，实现对单个	[20]
	剪切引导序列阵列体	VSG的高水平表达
	NUFIP剪切因子体
	DNA聚合酶IE	调节VSG切换	[21]
	共济失调毛细血管扩张和Rad3相关激酶		[22]
	组蛋白甲基转移酶DOT1B及其互作		[23]
	蛋白RNA酶H2
	阻遏物激活蛋白1		[24]
	同源重组酶RAD51		[25]
	同源重组酶RAD50		[26]
	转录激活子		[27]
转录后水平 Posttranscriptional level	ploy(A)尾巴中腺苷进行甲基化修饰	增强VSG mRNA的稳定性	[28]
转录后水平 Posttranscriptional level	细胞周期蛋白F盒蛋白2及其互作蛋白	形成RNA结合复合体，增强VSG mRNA稳定	[29-32]

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

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