间日疟原虫入侵网织红细胞相关蛋白的研究进展

doi:10.12140/j.issn.1000-7423.2022.03.018

中国寄生虫学与寄生虫病杂志 ›› 2022, Vol. 40 ›› Issue (3): 396-401.doi: 10.12140/j.issn.1000-7423.2022.03.018

间日疟原虫入侵网织红细胞相关蛋白的研究进展

石天琪(), 陈军虎()

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）,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,卫生部寄生虫病原与媒介生物学重点实验室,上海 200025

收稿日期:2021-12-27 修回日期:2022-03-13 出版日期:2022-06-30 发布日期:2022-07-06
通讯作者: 陈军虎
作者简介:石天琪（1997-）,女,硕士研究生,从事寄生虫病防治研究。E-mail： 761561107@qq.com
基金资助:
上海市公共卫生体系建设三年行动计划(2020-2022)重点学科(GWV-10.1-XK13);上海市国际科技合作基金(18490741100)

Research progress on reticulocyte binding proteins associated with Plasmodium vivax invasion of reticulocytes

SHI Tian-qi(), CHEN Jun-hu()

National Institute of Plarasitic 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

Received:2021-12-27 Revised:2022-03-13 Online:2022-06-30 Published:2022-07-06
Contact: CHEN Jun-hu
Supported by:
Fifth Round of Three-Year Public Health Action Plan of Shanghai(GWV-10.1-XK13);Project of Shanghai Science and Technology Commission(18490741100)

摘要/Abstract

摘要：

间日疟原虫是世界上分布最广泛的疟原虫,也是造成非洲以外地区人群感染疟疾的主要原因。间日疟原虫优先入侵网织红细胞,呈现高度的种特异性。间日疟原虫网织红细胞结合蛋白（PvRBP）家族作为入侵配体,介导了间日疟原虫入侵网织红细胞的新途径,是重要的免疫靶点。其中PvRBP2b与转铁蛋白受体1（TfR1）,PvRBP2a与CD98的相互作用对间日疟原虫入侵网织红细胞至关重要。Pvrbp家族具有高度多态性并且可产生免疫逃避,能够增加间日疟入侵的效率和致病的严重程度。随着对间日疟原虫入侵分子机制研究的日益加深,研究产生高滴度抗体的疟疾疫苗将成为有效预防和控制疟疾的关键方法。本文就网织红细胞在间日疟原虫感染中的作用,以及PvRBP家族在人群产生免疫应答的研究进展作一综述。

关键词: 间日疟原虫, 入侵, 网织红细胞结合蛋白, 自然获得性免疫

Abstract:

Plasmodium vivax is the most geographically widespread malaria parasite that causes most malaria infection cases outside the most malarious continent, sub-Saharan Africa. P. vivax preferentially invades reticulocytes, with a high species specificity. P. vivax reticulocyte binding protein (PvRBP) family has been implicated in roles in reticulocyte invasion and severity of P. vivax infections. The members of PvRBP family act as invasion ligands that mediate new pathways for the parasites to invade reticulocytes, and therefore, are considered important immune targets. Importantly, PvRBP2a-CD98 and PvRBP2b-TfR1 have been identified as two major ligand-receptor pairs implicated in the invasion of reticulocytes by P. vivax. The Pvrbp family is highly polymorphic and can generate immune evasion, which can increase the efficiency of vivax malaria invasion and the severity of the disease. With the advances in research on the molecular mechanisms of P. vivax invasion, insights have been provided on members of this protein family as promising antimalarial vaccine candidates, able to generate high titer antibodies for effective prevention and control of vivax malaria. This review summarizes the role of reticulocytes in P. vivax infection and the function of the PvRBP proteins family as immune targets in the human population.

Key words: Plasmodium vivax, Reticulocyte binding protein, Invasion, Natural acquired immunity

中图分类号:

R382.311

石天琪, 陈军虎. 间日疟原虫入侵网织红细胞相关蛋白的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(3): 396-401.

SHI Tian-qi, CHEN Jun-hu. Research progress on reticulocyte binding proteins associated with Plasmodium vivax invasion of reticulocytes[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2022, 40(3): 396-401.

图/表 1

参考文献 61

[1]	WHO. World malaria report 2021[M]. Geneva: WHO, 2021: 17.
[2]	Fola AA,, Harrison GLA,, Hazairin MH, et al. Higher complexity of infection and genetic diversity of Plasmodium vivax than Plasmodium falciparum across all malaria transmission zones of Papua New Guinea[J]. Am J Trop Med Hyg, 2017, 96(3): 630-641.
[3]	Guerra CA,, Howes RE,, Patil AP, et al. The international limits and population at risk of Plasmodium vivax transmission in 2009[J]. PLoS Negl Trop Dis, 2010, 4(8): e774.
[4]	Zhang XX,, Chu RL,, Xuan YH, et al. Research progress on proteins associated with Plasmodium vivax invasion of erythrocytes[J]. Chin J Parasitol Parasit Dis, 2018, 36(2): 161-165. (in Chinese)
[4]	( 张馨心,, 楚瑞林,, 玄英花, 等. 间日疟原虫入侵红细胞的相关蛋白研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(2): 161-165.)
[5]	Zhang L,, YI BY,, Xia ZG, et al. Epidemiological characteristics of malaria in China, 2021[J]. Chin J Parasitol Parasit Dis, 2022, 40(2): 135-139. (in Chinese)
[5]	( 张丽,, 易博禹,, 夏志贵, 等. 2021年全国疟疾疫情特征分析[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(2): 135-139.)
[6]	Feng J,, Zhang L,, Tu H, et al. From elimination to post-elimination: characteristics, challenges and re-transmission preventing strategy of imported malaria in China[J]. Chin Trop Med, 2021, 21(1): 5-10. (in Chinese)
[6]	( 丰俊,, 张丽,, 涂宏, 等. 从消除到消除后: 中国输入性疟疾的疫情特征、挑战及防止再传播策略[J]. 中国热带医学, 2021, 21(1): 5-10.)
[7]	Cao J,, Liu YB,, Cao YY, et al. Sustained challenge to malaria elimination in China: imported malaria[J]. Chin J Parasitol Parasit Dis, 2018, 36(2): 93-96. (in Chinese)
[7]	( 曹俊,, 刘耀宝,, 曹园园, 等. 中国消除疟疾的持续挑战:输入性疟疾[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(2): 93-96.)
[8]	Cowman AF,, Tonkin CJ,, Tham WH, et al. The molecular basis of erythrocyte invasion by malaria parasites[J]. Cell Host Microbe, 2017, 22(2): 232-245.
[9]	Pasvol G,, Weatherall DJ,, Wilson RJ. The increased susceptibility of young red cells to invasion by the malarial parasite Plasmodium falciparum[J]. Br J Haematol, 1980, 45(2): 285-295.
[10]	Mitchell GH,, Hadley TJ,, McGinniss MH, et al. Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors[J]. Blood, 1986, 67(5): 1519-1521.
[11]	Griffiths RE,, Kupzig S,, Cogan N, et al. The ins and outs of human reticulocyte maturation: autophagy and the endosome/exosome pathway[J]. Autophagy, 2012, 8(7): 1150-1151.
[12]	Lim C,, Pereira L,, Saliba KS, et al. Reticulocyte preference and stage development of Plasmodium vivax isolates[J]. J Infect Dis, 2016, 214(7): 1081-1084.
[13]	Chitnis CE,, Sharma A. Targeting the Plasmodium vivax Duffy-binding protein[J]. Trends Parasitol, 2008, 24(1): 29-34.
[14]	Ovchynnikova E,, Aglialoro F,, Bentlage AEH, et al. DARC extracellular domain remodeling in maturating reticulocytes explains Plasmodium vivax tropism[J]. Blood, 2017, 130(12): 1441-1444.
[15]	Kaur H,, Sehgal R,, Rani S. Duffy antigen receptor for chemokines (DARC) and susceptibility to Plasmodium vivax malaria[J]. Parasitol Int, 2019, 71: 73-75.
[16]	Gruszczyk J,, Kanjee U,, Chan LJ, et al. Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax[J]. Science, 2018, 359(6371): 48-55.
[17]	Kanjee U,, Rangel GW,, Clark MA, et al. Molecular and cellular interactions defining the tropism of Plasmodium vivax for reticulocytes[J]. Curr Opin Microbiol, 2018, 46: 109-115.
[18]	Galinski MR,, Medina CC,, Ingravallo P, et al. A reticulocyte-binding protein complex of Plasmodium vivax merozoites[J]. Cell, 1992, 69(7): 1213-1226.
[19]	Galinski MR,, Xu M,, Barnwell JW. Plasmodium vivax reticulocyte binding protein-2 (PvRBP-2) shares structural features with PvRBP-1 and the Plasmodium yoelii 235 kDa rhoptry protein family[J]. Mol Biochem Parasitol, 2000, 108(2): 257-262.
[20]	Urquiza M,, Patarroyo MA,, Marí V, et al. Identification and polymorphism of Plasmodium vivax RBP-1 peptides which bind specifically to reticulocytes[J]. Peptides, 2002, 23(12): 2265-2277.
[21]	Gaur D,, Singh S,, Singh S,, et al. Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds to erythrocytes and blocks invasion[J]. Proc Natl Acad Sci USA, 2007, 104(45): 17789-17794.
[22]	Carlton JM,, Adams JH,, Silva JC, et al. Comparative genomics of the neglected human malaria parasite Plasmodium vivax[J]. Nature, 2008, 455(7214): 757-763.
[23]	Li J,, Han ET. Dissection of the Plasmodium vivax reticulocyte binding-like proteins (PvRBPs)[J]. Biochem Biophys Res Commun, 2012, 426(1): 1-6.
[24]	Hester J,, Chan ER,, Menard D, et al. De novo assembly of a field isolate genome reveals novel Plasmodium vivax erythrocyte invasion genes[J]. PLoS Negl Trop Dis, 2013, 7(12): e2569.
[25]	Gupta ED,, Anand G,, Singh H, et al. Naturally acquired human antibodies against reticulocyte-binding domains of Plasmodium vivax proteins, PvRBP2c and PvRBP1a, exhibit binding-inhibitory activity[J]. J Infect Dis, 2017, 215(10): 1558-1568.
[26]	França CT,, He WQ,, Gruszczyk J, et al. Plasmodium vivax reticulocyte binding proteins are key targets of naturally acquired immunity in young Papua new Guinean children[J]. PLoS Negl Trop Dis, 2016, 10(9): e0005014.
[27]	Chim-Ong A,, Surit T,, Chainarin S, et al. The blood stage antigen RBP2-P1 of Plasmodium vivax binds reticulocytes and is a target of naturally acquired immunity[J]. Infect Immun, 2020, 88(4): e00616-e00619.
[28]	Han JH,, Lee SK,, Wang B, et al. Identification of a reticulocyte-specific binding domain of Plasmodium vivax reticulocyte-binding protein 1 that is homologous to the PfRh4 erythrocyte-binding domain[J]. Sci Rep, 2016, 6: 26993.
[29]	Han JH,, Lee SK,, Wang B, et al. Identification of a reticulocyte-specific binding domain of Plasmodium vivax reticulocyte-binding protein 1 that is homologous to the PfRh4 erythrocyte-binding domain[J]. Sci Rep, 2016, 6: 26993.
[30]	Ntumngia FB,, Thomson-Luque R,, Galusic S, et al. Identification and immunological characterization of the ligand domain of Plasmodium vivax reticulocyte binding protein 1a[J]. J Infect Dis, 2018, 218(7): 1110-1118.
[31]	Gupta S,, Singh S,, Popovici J, et al. Targeting a reticulocyte binding protein and Duffy binding protein to inhibit reticulocyte invasion by Plasmodium vivax[J]. Sci Rep, 2018, 8: 10511.
[32]	Rayner JC,, Galinski MR,, Ingravallo P, et al. Two Plasmodium falciparum genes express merozoite proteins that are related to Plasmodium vivax and Plasmodium yoelii adhesive proteins involved in host cell selection and invasion[J]. Proc Natl Acad Sci USA, 2000, 97(17): 9648-9653.
[33]	Chan LJ,, Dietrich MH,, Nguitragool W, et al. Plasmodium vivax reticulocyte binding proteins for invasion into reticulocytes[J]. Cell Microbiol, 2020, 22(1): e13110.
[34]	Malleret B,, Sahili AE,, Tay MZ, et al. Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells[J]. Nat Microbiol, 2021, 6(8): 991-999.
[35]	Wright KE,, Hjerrild KA,, Bartlett J, et al. Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies[J]. Nature, 2014, 515(7527): 427-430.
[36]	Gruszczyk J,, Lim NTY,, Arnott A, et al. Structurally conserved erythrocyte-binding domain in Plasmodium provides a versatile scaffold for alternate receptor engagement[J]. Proc Natl Acad Sci USA, 2016, 113(2): E191-E200.
[37]	Gruszczyk J,, Huang RK,, Chan LJ, et al. Cryo-EM structure of an essential Plasmodium vivax invasion complex[J]. Nature, 2018, 559(7712): 135-139.
[38]	Galinski MR,, Barnwell JW. Plasmodium vivax: merozoites, invasion of reticulocytes and considerations for malaria vaccine development[J]. Parasitol Today, 1996, 12(1): 20-29.
[39]	Ford A,, Kepple D,, Abagero BR, et al. Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes[J]. PLoS Negl Trop Dis, 2020, 14(10): e0008234.
[40]	Kosaisavee V,, Lek-Uthai U,, Suwanarusk R, et al. Genetic diversity in new members of the reticulocyte binding protein family in Thai Plasmodium vivax isolates[J]. PLoS One, 2012, 7(3): e32105.
[41]	Han JH,, Li J,, Wang B, et al. Identification of immunodominant B-cell epitope regions of reticulocyte binding proteins in Plasmodium vivax by protein microarray based immunoscreening[J]. Korean J Parasitol, 2015, 53(4): 403-411.
[42]	Ovchynnikova E,, Aglialoro F,, Bentlage AEH, et al. DARC extracellular domain remodeling in maturating reticulocytes explains Plasmodium vivax tropism[J]. Blood, 2017, 130(12): 1441-1444.
[43]	Kanjee U,, Rangel GW,, Clark MA, et al. Molecular and cellular interactions defining the tropism of Plasmodium vivax for reticulocytes[J]. Curr Opin Microbiol, 2018, 46: 109-115.
[44]	Moras M,, Lefevre SD,, Ostuni MA. From erythroblasts to mature red blood cells: organelle clearance in mammals[J]. Front Physiol, 2017, 8: 1076.
[45]	Thomson-Luque R,, Wang CQ,, Ntumngia FB, et al. In-depth phenotypic characterization of reticulocyte maturation using mass cytometry[J]. Blood Cells Mol Dis, 2018, 72: 22-33.
[46]	Lawrence CM,, Ray S,, Babyonyshev M, et al. Crystal structure of the ectodomain of human transferrin receptor[J]. Science, 1999, 286(5440): 779-782.
[47]	Kawabata H. Transferrin and transferrin receptors update[J]. Free Radic Biol Med, 2019, 133: 46-54.
[48]	Cheng YF,, Zak O,, Aisen P, et al. Structure of the human transferrin receptor-transferrin complex[J]. Cell, 2004, 116(4): 565-576.
[49]	Chan LJ,, Gandhirajan A,, Carias LL, et al. Naturally acquired blocking human monoclonal antibodies to Plasmodium vivax reticulocyte binding protein 2b[J]. Nat Commun, 2021, 12(1): 1538.
[50]	Malleret B,, Rénia L,, Russell B. The unhealthy attraction of Plasmodium vivax to reticulocytes expressing transferrin receptor 1 (CD71)[J]. Int J Parasitol, 2017, 47(7): 379-383.
[51]	Segawa H,, Fukasawa Y,, Miyamoto K, et al. Identification and functional characterization of a Na⁺-independent neutral amino acid transporter with broad substrate selectivity[J]. J Biol Chem, 1999, 274(28): 19745-19751.
[52]	Malleret B,, Li A,, Zhang R, et al. Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes[J]. Blood, 2015, 125(8): 1314-1324.
[53]	Mueller I,, Galinski MR,, Tsuboi T, et al. Natural acquisition of immunity to Plasmodium vivax: epidemiological observations and potential targets[J]. Adv Parasitol, 2013, 81: 77-131.
[54]	Céspedes N,, Li Wai Suen CSN,, Koepfli C, et al. Natural immune response to Plasmodium vivax alpha-helical coiled coil protein motifs and its association with the risk of P. vivax malaria[J]. PLoS One, 2017, 12(6): e0179863.
[55]	Tran TM,, Oliveira-Ferreira J,, Moreno A, et al. Comparison of IgG reactivities to Plasmodium vivax merozoite invasion antigens in a Brazilian Amazon population[J]. Am J Trop Med Hyg, 2005, 73(2): 244-255.
[56]	França CT,, White MT,, He WQ, et al. Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development[J]. eLife, 2017, 6: e28673.
[57]	Longley RJ,, França CT,, White MT, et al. Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand[J]. Malar J, 2017, 16(1): 178.
[58]	Chuquiyauri R,, Molina DM,, Moss EL, et al. Genome-scale protein microarray comparison of human antibody responses in Plasmodium vivax relapse and reinfection[J]. Am J Trop Med Hyg, 2015, 93(4): 801-809.
[59]	Longley RJ,, White MT,, Takashima E, et al. Development and validation of serological markers for detecting recent Plasmodium vivax infection[J]. Nat Med, 2020, 26(5): 741-749.
[60]	Hietanen J,, Chim-Ong A,, Chiramanewong T, et al. Gene models, expression repertoire, and immune response of Plasmodium vivax reticulocyte binding proteins[J]. Infect Immun, 2015, 84(3): 677-685.
[61]	Chen SL,, Liu TP,, Xu WY. Development of malaria vaccines and the challenges[J]. Chin J Parasitol Parasit Dis, 2021, 39(3): 283-295. (in Chinese)
[61]	( 陈穗林,, 刘太平,, 徐文岳. 疟疾疫苗研制及其存在的问题[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(3): 283-295.)

间日疟原虫入侵网织红细胞相关蛋白的研究进展

Research progress on reticulocyte binding proteins associated with Plasmodium vivax invasion of reticulocytes

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 1

参考文献 61

相关文章 15

编辑推荐

Metrics

本文评价

[1]	杨晚璇, 沈海默, 陈绅波, 陈军虎. 间日疟原虫VIR14蛋白与ICAM-1受体相互作用关键位点分析[J]. 中国寄生虫学与寄生虫病杂志, 2025, 43(2): 192-197.
[2]	丁红芸, 董莹, 徐艳春, 邓艳, 刘言, 吴静, 陈梦妮, 张苍林. 云南省输入性间日疟原虫多药抗性蛋白1基因突变多态性分析[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(4): 404-411.
[3]	张小涵, 冯颖, 陈冉, 桑晓宇, 杨娜. 弓形虫类锥体结构、功能及调控机制的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(6): 832-835.
[4]	金行一, 张玲玲, 朱素娟, 徐卫民, 陈珺芳, 阮卫, 姚立农, 陈华良. 间日疟原虫裂殖子表面蛋白1和环子孢子蛋白基因多态性分析[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(3): 323-331.
[5]	徐艳春, 董莹, 邓艳, 毛祥华, 陈梦妮, 张苍林, 江陆斌. 云南省不同感染来源间日疟原虫环子孢子蛋白基因多态和种群结构分析[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(1): 67-73.
[6]	董莹, 邓艳, 陈梦妮, 徐艳春, 毛祥华, 王剑, 孙艾明, 薛靖波. 不同感染来源间日疟原虫抗叶酸类药物相关基因的研究[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(2): 103-111.
[7]	张馨心, 楚瑞林, 玄英花, 程洋. 间日疟原虫入侵红细胞的相关蛋白研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(2): 161-165.
[8]	董莹, 孙艾明, 陈梦妮, 徐艳春, 毛祥华, 邓艳. 云南省输入性及本地感染间日疟原虫裂殖子表面蛋白1基因5区序列的多态性分析[J]. 中国寄生虫学与寄生虫病杂志, 2017, 35(1): 1-7.
[9]	张苍林，周红宁，聂仁华，刘慧，王剑，李春富，杨亚明*. 云南省边境地区疟原虫18S rRNA基因种类鉴定与序列分析[J]. 中国寄生虫学与寄生虫病杂志, 2016, 34(3): 7-220-226.
[10]	王加志1，尹雪梅1，李希尚1，尹授钦1，丰俊2*. 一个红细胞内同时寄生不同期间日疟原虫输入性病例1例[J]. 中国寄生虫学与寄生虫病杂志, 2016, 34(3): 20-290-292.
[11]	刘颖，钱丹，陈伟奇，周瑞敏，杨成运，赵玉玲，许汴利，张红卫*. 环子孢子蛋白基因检测法对1例间日疟病例的溯源[J]. 中国寄生虫学与寄生虫病杂志, 2015, 33(2): 19-156-178.
[12]	王真瑜，江莉，张耀光，张小萍，蔡黎*. 两种疟疾快速诊断试剂盒检测效果的比较[J]. 中国寄生虫学与寄生虫病杂志, 2014, 32(1): 11-50-53.
[13]	徐超, 徐秀来, 黄炳成. 间日疟原虫裂殖子表面蛋白3α基因多态性的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2013, 31(6): 12-473-476.
[14]	刘颖, 周瑞敏, 陈伟奇, 钱丹, 赵玉玲, 赵旭东, 许汴利, 苏云普, 张红卫. 间日疟原虫环子孢子蛋白PCR-RFLP多态性分析[J]. 中国寄生虫学与寄生虫病杂志, 2013, 31(6): 17-483-485.
[15]	胡明洁1，方强2 *，吴守伟1，汤必奎1，张静1，焦玉萌2，夏惠2，沈继龙3. 间日疟原虫安徽地域株乳酸脱氢酶基因序列同源性分析[J]. 中国寄生虫学与寄生虫病杂志, 2013, 31(2): 20-148-150.