恶性疟原虫感染红细胞表面STEVOR蛋白的结构和功能研究进展

doi:10.20199/j.issn.1672-2302.2025.02.012

热带病与寄生虫学 ›› 2025, Vol. 23 ›› Issue (2): 125-130.doi: 10.20199/j.issn.1672-2302.2025.02.012

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恶性疟原虫感染红细胞表面STEVOR蛋白的结构和功能研究进展

孙芷珊¹(), 尹静娴¹, 赵翰卿¹, 朱银山¹, 周晓农¹^,²^,³, 陈军虎¹^,²^,³()

1.上海交通大学医学院-国家热带病研究中心全球健康学院，上海 200025
2.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，科技部国家级热带病国际联合研究中心
3.海南热带病研究中心（国家热带病研究中心海南分中心）

收稿日期:2024-10-18 出版日期:2025-04-20 发布日期:2025-06-04
通信作者: 陈军虎，E-mail: chenjh@nipd.chinacdc.cn
作者简介:孙芷珊，女，硕士在读，研究方向：寄生虫病防治。E-mail: lofia1007@sjtu.edu.cn
基金资助:
上海市自然科学基金项目(24ZR1473200);上海市加强公共卫生体系建设三年行动计划（2023—2025年）项目(GWVI-11.1-12);上海市加强公共卫生体系建设三年行动计划（2023—2025年）项目(GWVI-11.2-XD33)

Research progress on the structure and function of STEVOR proteins on Plasmodium falciparum-infected red blood cells

SUN Zhishan¹(), YIN Jingxian¹, ZHAO Hanqing¹, ZHU Yinshan¹, ZHOU Xiaonong¹^,²^,³, Kassegne Kokouvi¹, CHEN Junhu¹^,²^,³()

1. School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
2. National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Health Commission Key Laboratory of Parasite and Vector Biology, World Health Organization Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology
3. Hainan Tropical Diseases Research Center (Hainan Sub-center, Chinese Center for Tropical Diseases Research)

Received:2024-10-18 Online:2025-04-20 Published:2025-06-04
Contact: CHEN Junhu, E-mail：chenjh@nipd.chinacdc.cn

摘要/Abstract

摘要：

恶性疟原虫感染的红细胞表面表达的变异表面抗原（variant surface antigens, VSAs）与重症疟疾的发病有关，可作为保护性免疫的潜在靶点。作为VSAs家族的重要成员，亚端粒变体开放阅读框（subtelomeric variant open reading frame, STEVOR）不仅介导疟原虫裂殖子对红细胞的入侵，而且能与红细胞表面的糖蛋白C（glycophorin C, GPC）受体结合，在玫瑰花结的形成中发挥重要作用。针对STEVOR半保守（semiconserved, SC）区的抗体可以抑制裂殖子的入侵和玫瑰花结的形成。本文对STEVOR的结构和功能进行系统总结，探讨了其在重症疟疾中的作用机制以及相关的疫苗研究进展，从而为重症疟疾的防治提供参考。

关键词: 恶性疟原虫, STEVOR, 黏附, 玫瑰花结, 免疫逃避

Abstract:

The variant surface antigens (VSAs) present on Plasmodium falciparum-infected erythrocytes are implicated in the pathogenesis of severe malaria, and can serve as a potential target for protective immunity. The subtelomeric variant open reading frame (STEVOR) is a significant member of the VSAs family, which mediates the invasion of uninfected erythrocytes by merozoites and binding to glycophorin C (GPC) receptors on the erythrocyte surface and plays a crucial role in rosetting formation. Antibodies targeting the semiconserved (SC) region of STEVOR have been shown to inhibit both merozoite invasion and rosette formation. This article aims at systematically summarizing the structure and function of STEVOR, investigating the action mechanism of STEVOR in severe malaria and reviewing its progress in related vaccine development, with an attempt to provide a reference for the prevention and control of severe malaria.

Key words: Plasmodium falciparum, STEVOR, Adhesion, Rosetting, Immune escape

中图分类号:

R382.3+1

孙芷珊, 尹静娴, 赵翰卿, 朱银山, 周晓农, 陈军虎. 恶性疟原虫感染红细胞表面STEVOR蛋白的结构和功能研究进展[J]. 热带病与寄生虫学, 2025, 23(2): 125-130.

SUN Zhishan, YIN Jingxian, ZHAO Hanqing, ZHU Yinshan, ZHOU Xiaonong, Kassegne Kokouvi, CHEN Junhu. Research progress on the structure and function of STEVOR proteins on Plasmodium falciparum-infected red blood cells[J]. Journal of Tropical Diseases and Parasitology, 2025, 23(2): 125-130.

图/表 2

参考文献 45

[1]	Crider K, Williams J, Qi YP, et al. Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas[J]. Cochrane Database Syst Rev, 2022, 2(2022):CD014217.
[2]	World Health Organization. World malaria report 2024: addressing inequity in the global malaria response[R]. Geneva: World Health Organization, 2024.
[3]	World Health Organization. Malaria[EB/OL]. (2023-12-04)[2024-09-20]. https://www.who.int/news-room/fact-sheets/detail/malaria.
[4]	Venugopal K, Hentzschel F, Valkiūnas G, et al. Plasmodium asexual growth and sexual development in the haematopoietic niche of the host[J]. Nat Rev Microbiol, 2020, 18(3):177-189. doi: 10.1038/s41579-019-0306-2 pmid: 31919479
[5]	国家传染病医学中心撰写组. 疟疾诊疗指南[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(4):419-427. doi: 10.12140/j.issn.1000-7423.2022.04.001
[6]	Chew M, Ye WJ, Omelianczyk RI, et al. Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo[J]. Nat Commun, 2022, 13(1):4067.
[7]	Wahlgren M, Goel S, Akhouri RR. Variant surface antigens of Plasmodium falciparum and their roles in severe malaria[J]. Nat Rev Microbiol, 2017, 15(8):479-491. doi: 10.1038/nrmicro.2017.47 pmid: 28603279
[8]	曹伟, 王一, 张熙致, 等. 脑型疟辅助治疗研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(3):361-373,379. doi: 10.12140/j.issn.1000-7423.2023.03.016
[9]	Zakama AK, Ozarslan N, Gaw SL. Placental malaria[J]. Curr Trop Med Rep, 2020, 7(4):162-171.
[10]	Niang M, Bei AK, Madnani KG, et al. STEVOR is a Plasmodium falciparum erythrocyte binding protein that mediates merozoite invasion and rosetting[J]. Cell Host Microbe, 2014, 16(1):81-93.
[11]	Niang M, Yan Yam X, Preiser PR. The Plasmodium falciparum STEVOR multigene family mediates antigenic variation of the infected erythrocyte[J]. PLoS Pathog, 2009, 5(2):e1000307.
[12]	Tibúrcio M, Niang M, Deplaine G, et al. A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stages[J]. Blood, 2012, 119(24):e172-80.
[13]	Limpaiboon T, Taylor DW, Jones G, et al. Characterization of a Plasmodium falciparum epitope recognized by a monoclonal antibody with broad isolate and species specificity[J]. Southeast Asian J Trop Med Public Health, 1991, 22(2):284.
[14]	Blythe JE, Yam XY, Kuss C, et al. Plasmodium falciparum STEVOR proteins are highly expressed in patient isolates and located in the surface membranes of infected red blood cells and the apical tips of merozoites[J]. Infect Immun, 2008, 76(7):3329-3336. doi: 10.1128/IAI.01460-07 pmid: 18474651
[15]	Blythe JE, Surentheran T, Preiser PR. STEVOR: a multifunctional protein?[J]. Mol Biochem Parasitol, 2004, 134(1):11-15.
[16]	Stephan Wichers J, Scholz JAM, Strauss J, et al. Dissecting the gene expression,localization,membrane topology,and function of the Plasmodium falciparum STEVOR protein family[J]. mBio, 2019, 10(4):e01500-19.
[17]	Bachmann A, Petter M, Tilly AK, et al. Temporal expression and localization patterns of variant surface antigens in clinical Plasmodium falciparum isolates during erythrocyte schizogony[J]. PLoS One, 2012, 7(11):e49540.
[18]	Kaur J, Hora R. ‘2TM proteins’: an antigenically diverse superfamily with variable functions and export pathways[J]. PeerJ, 2018,6:e4757.
[19]	Boddey JA, O' Neill MT, Lopaticki S, et al. Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding[J]. Nat Commun, 2016,7:10470.
[20]	Lavazec C, Sanyal S, Templeton TJ. Hypervariability within the rifin,stevor and pfmc-2TM superfamilies in Plasmodium falciparum[J]. Nucleic Acids Res, 2006, 34(22):6696-6707.
[21]	Bachmann A, Scholz JAM, Janßen M, et al. A comparative study of the localization and membrane topology of members of the RIFIN,STEVOR and PfMC-2TM protein families in Plasmodium falciparum-infected erythrocytes[J]. Malar J, 2015, 14:274.
[22]	Andersson A, Kudva R, Magoulopoulou A, et al. Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite[J]. FEBS J, 2020, 287(13):2744-2762. doi: 10.1111/febs.15171 pmid: 31821735
[23]	Kaviratne M, Khan SM, Jarra W, et al. Small variant STEVOR antigen is uniquely located within Maurer′s clefts in Plasmodium falciparum-infected red blood cells[J]. Eukaryot Cell, 2002, 1(6):926-935. doi: 10.1128/EC.1.6.926-935.2002 pmid: 12477793
[24]	McHugh E, Carmo OMS, Blanch A, et al. Role of Plasmodium falciparum protein GEXP07 in maurer′s cleft morphology,knob architecture,and P. falciparum EMP1 trafficking[J]. mBio, 2020, 11(2):e03320-19.
[25]	Zhou AE, Berry AA, Bailey JA, et al. Antibodies to peptides in semiconserved domains of RIFINs and STEVORs correlate with malaria exposure[J]. mSphere, 2019, 4(2):e00097-19.
[26]	García JE, Puentes A, Curtidor H, et al. Peptides from the Plasmodium falciparum STEVOR putative protein bind with high affinity to normal human red blood cells[J]. Peptides, 2005, 26(7):1133-1143.
[27]	Khattab A, Bonow I, Schreiber N, et al. Plasmodium falciparum variant STEVOR antigens are expressed in merozoites and possibly associated with erythrocyte invasion[J]. Malar J, 2008,7:137.
[28]	Lee WC, Russell B, Rénia L. Evolving perspectives on rosetting in malaria[J]. Trends Parasitol, 2022, 38(10):882-889.
[29]	Singh H, Madnani K, Lim YB, et al. Expression dynamics and physiologically relevant functional study of STEVOR in asexual stages of Plasmodium falciparum infection[J]. Cell Microbiol, 2017, 19(6):e12715.
[30]	Sanyal S, Egée S, Bouyer G, et al. Plasmodium falciparum STEVOR proteins impact erythrocyte mechanical properties[J]. Blood, 2012, 119(2):e1-8.
[31]	Ramdani G, Naissant B, Thompson E, et al. cAMP-signalling regulates gametocyte-infected erythrocyte deformability required for malaria parasite transmission[J]. PLoS Pathog, 2015, 11(5):e1004815.
[32]	Naissant B, Dupuy F, Duffier Y, et al. Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission[J]. Blood, 2016, 127(24):e42-53.
[33]	Arora G, Hart GT, Manzella-Lapeira J, et al. NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity[J]. Elife, 2018,7:e36806.
[34]	Jake Gonzales S, Reyes RA, Braddom AE, et al. Naturally acquired humoral immunity against Plasmodium falciparum malaria[J]. Front Immunol, 2020, 11:594653.
[35]	Kanoi BN, Nagaoka H, White MT, et al. Global repertoire of human antibodies against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a malaria exposed population[J]. Front Immunol, 2020, 11:893.
[36]	Travassos MA, Niangaly A, Bailey JA, et al. Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets[J]. Sci Rep, 2018, 8(1):6281. doi: 10.1038/s41598-018-24462-4 pmid: 29674705
[37]	Etefia E, Etoh PI. Malaria vaccine development:challenges and prospects[J]. Med Pharm J, 2023, 2(1):28-42.
[38]	Uno N, Ross TM. Multivalent next generation influenza virus vaccines protect against seasonal and pre-pandemic viruses[J]. Sci Rep, 2024, 14(1):1440.
[39]	Pandey RK, Bhatt TK, Prajapati VK. Novel immunoinformatics approaches to design multi-epitope subunit vaccine for malaria by investigating Anopheles salivary protein[J]. Sci Rep, 2018, 8(1):1125. doi: 10.1038/s41598-018-19456-1 pmid: 29348555
[40]	Atapour A, Vosough P, Jafari S, et al. A multi-epitope vaccine designed against blood-stage of malaria: an immunoinformatic and structural approach[J]. Sci Rep, 2022, 12(1):11683. doi: 10.1038/s41598-022-15956-3 pmid: 35804032
[41]	Maharaj L, Adeleke VT, Fatoba AJ, et al. Immunoinformatics approach for multi-epitope vaccine design against P. falciparum malaria[J]. Infect Genet Evol, 2021, 92:104875.
[42]	Chan JA, Fowkes FJI, Beeson JG. Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates[J]. Cell Mol Life Sci, 2014, 71(19):3633-3657.
[43]	Bustamante LY, Josefin Bartholdson S, Crosnier C, et al. A full-length recombinant Plasmodium falciparum PfRH5 protein induces inhibitory antibodies that are effective across common PfRH5 genetic variants[J]. Vaccine, 2013, 31(2):373-379. doi: 10.1016/j.vaccine.2012.10.106 pmid: 23146673
[44]	Arunachalam PS, Ha N, Moses Dennison S, et al. A comparative immunological assessment of multiple clinical-stage adjuvants for the R21 malaria vaccine in nonhuman Primates[J]. Sci Transl Med, 2024, 16(758):eadn6605.
[45]	Datoo MS, Dicko A, Tinto H, et al. Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial[J]. Lancet, 2024, 403(10426):533-544. doi: 10.1016/S0140-6736(23)02511-4 pmid: 38310910

恶性疟原虫感染红细胞表面STEVOR蛋白的结构和功能研究进展

Research progress on the structure and function of STEVOR proteins on Plasmodium falciparum-infected red blood cells

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