疟原虫纳虫空泡膜功能及其相关蛋白的研究进展

doi:10.12140/j.issn.1000-7423.2022.03.019

摘要/Abstract

摘要：

疟疾是威胁全球人类健康的重要传染病之一。如何抑制疟疾的传播,仍然是一个亟待解决的问题。当疟原虫入侵宿主细胞后,会在胞内生长、繁殖,造成严重的病理损伤。而纳虫空泡膜作为宿主细胞与疟原虫直接接触的界面,对疟原虫生存状态有重要意义。本文简要介绍了疟原虫纳虫空泡膜的形成及其与疟原虫细胞质质膜、管状囊泡网络之间的关联,对红内期、肝内期与有性期纳虫空泡膜相关蛋白及其功能进行归纳总结,并对疟疾防治策略提出了展望。

关键词: 疟原虫, 纳虫空泡膜, 膜蛋白, 疟疾

Abstract:

Malaria is one of the most important infectious diseases in the world and seriously threatens human health. It remains a critical problem to interrupt malaria transmission. Plasmodium parasites invade and multiply inside the host cells causing severe pathological damage to the host. As the interface between the host cells and Plasmodium parasites, PVM is of crucial importance for the survival of Plasmodium parasites. This manuscript briefly introduces the formation of PVM and its relationship with PPM and TVN. The PVM-associated proteins and their functions in blood-stage, liver-stage and sexual-stage parasites are summarized. This review also presents perspectives on malaria control strategies.

Key words: Plasmodium, PVM, Membrane protein, Malaria

中图分类号:

R382.31

葛洁云, 刘蕾, 孙毅凡, 程洋. 疟原虫纳虫空泡膜功能及其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): 402-410.

GE Jie-yun, LIU Lei, SUN Yi-fan, CHENG Yang. Advances in research on the vacuolar membrane function and the associated proteins of plasmodium parasitophorous vacuole[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2022, 40(3): 402-410.

图/表 3

图1

图2

表1

疟原虫纳虫空泡膜相关蛋白及其功能

蛋白	PlasmoDB_ID	功能	参考文献
PfETRAMP5	PF3D7_0532100	与载脂蛋白相互作用,维持脂质稳态;可能与营养渗透与蛋白输出有关。	[24-25]
PfETRAMP10.2	PF3D7_1033200	参与恶性疟原虫的蛋白输出。	[26]
PfHSP101	PF3D7_1116800	对输出蛋白起解折叠酶和解聚酶的作用。	[35-36]
PfEXP1	PF3D7_1121600	是EXP2发挥营养渗透通道功能所必须的,可能在维持PVM结构方面发挥重要功能;作为谷胱甘肽转移酶发挥作用,解毒血红蛋白副产物。	[48,52]
PfEXP2	PF3D7_1471100	作为PVM营养渗透通道;作为PTEX的转运通道。	[38,46]
PfPTEX150	PF3D7_1436300	与EXP2共同形成PTEX的转运通道。	[38]
PfPTEX88	PF3D7_1105600	可能作为一种受体将输出蛋白移交给HSP101。	[39]
PfTRX2	PF3D7_1345100	通过保守的CXXC活性位点减少底物蛋白质中的二硫键,从而促进输出蛋白的转运。	[42]
PfRON3	PF3D7_1252100	与葡萄糖的摄入与PTEX的转运蛋白功能有关。	[44]
PfPV1	PF3D7_1129100	作为PTEX辅助分子,在蛋白输出中起重要作用。	[45]
PfCG2	PF3D7_0709300	可能与血红蛋白摄入与消化过程有关。	[53]
PfCLAG3.1	PF3D7_0302500	与疟原虫表面阴离子通道（PSAC）活性相关联。	[61]
PfCLAG3.2	PF3D7_0302200	与疟原虫表面阴离子通道（PSAC）活性相关联。	[61]
PfRhopH2	PF3D7_0929400	可能对NPP活性以及与血浆交换营养和代谢产物以促进疟原虫的生长和增殖很重要。	[59]
PF3D7_0402000	PF3D7_0402000	可能在调节PVM与红细胞膜结构中起作用。	[62]
Pfs16	PF3D7_0531200	对性期疟原虫的发育是重要的,敲除后配子体数目显著较少。	[75]
PfPEG3/MDV1	PF3D7_1216500	对配子体感染红细胞正常膜结构的形成起关键作用,敲除导致雄性配子体细胞显著减少。	[78]
PvETRAMP4	PVX_090230	高免疫原性蛋白。	[22]
PvETRAMP11.2	PVP01_0422600	高免疫原性蛋白。	[22]
PvUIS4	PVX_001715	可用于区别肝细胞内休眠子与活跃发育的裂殖子。	[72]
PbSEP1	PBANKA_0524800	维持伯氏疟原虫红内期发育。	[28]
PbSEP2	PBANKA_0524200	维持伯氏疟原虫红内期发育。	[28]
PbSEP3	PBANKA_0501100	维持伯氏疟原虫红内期发育。	[28]
PbEXP1	PBANKA_0926700	将肝细胞ApoH募集到PVM,并介导ApoH和ApoH相关蛋白及脂质的摄取。	[11]
PbUIS3	PBANKA_1400800	与肝脏脂肪酸结合蛋白L-FABP相互作用,对肝内期疟原虫的生长必不可少;竞争结合宿主细胞LC3,充当自噬抑制剂。	[66-67]
PbUIS4	PBANKA_0501200	与肝细胞中疟原虫蛋白质的输出有关。	[6]
PbPL	PBANKA_1128100	与裂殖子从肝细胞中的释放有关。	[69]
PbIBIS1	PBANKA_1365500	与肝细胞中疟原虫蛋白质的输出有关。	[6]
PBANKA_1003900	PBANKA_1003900	影响按蚊中肠内动合子的生存能力或卵囊的早期发育。	[76]
Pbpeg3/mdv1	PBANKA_1432200	敲除导致疟原虫形成受精卵的能力大大下降。	[80]

表1

参考文献 81

[1]	World Health Organization. World Malaria Report 2021[R]. Geneva: WHO, 2021.
[2]	Zhang L,, Feng J,, Tu H, et al. Malaria epidemiology in China in 2020[J]. Chin J Parasitol Parasit Dis, 2021, 39(2): 195-199. (in Chinese)
	( 张丽,, 丰俊,, 涂宏, 等. 2020年全国疟疾疫情分析[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(2): 195-199.)
[3]	Goldberg DE,, Zimmerberg J. Hardly vacuous: the parasitophorous vacuolar membrane of malaria parasites[J]. Trends Parasitol, 2020, 36(2): 138-146. doi: S1471-4922(19)30297-1 pmid: 31866184
[4]	Matz JM,, Beck JR,, Blackman MJ. The parasitophorous vacuole of the blood-stage malaria parasite[J]. Nat Rev Microbiol, 2020, 18(7): 379-391. doi: 10.1038/s41579-019-0321-3
[5]	Vaughan AM,, Kappe SHI. Malaria parasite liver infection and exoerythrocytic biology[J]. Cold Spring Harb Perspect Med, 2017, 7(6): a025486.
[6]	Ingmundson A,, Nahar C,, Brinkmann V, et al. The exported Plasmodium berghei protein IBIS1 delineates membranous structures in infected red blood cells[J]. Mol Microbiol, 2012, 83(6): 1229-1243. doi: 10.1111/j.1365-2958.2012.08004.x pmid: 22329949
[7]	Bannister LH,, Hopkins JM,, Fowler RE, et al. A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages[J]. Parasitol Today, 2000, 16(10): 427-433. pmid: 11006474
[8]	Meis JF,, Verhave JP,, Jap PH, et al. Ultrastructural observations on the infection of rat liver by Plasmodium berghei sporozoites in vivo[J]. J Protozool, 1983, 30(2): 361-366. doi: 10.1111/j.1550-7408.1983.tb02931.x
[9]	Nagao E,, Seydel KB,, Dvorak JA. Detergent-resistant erythrocyte membrane rafts are modified by a Plasmodium falciparum infection[J]. Exp Parasitol, 2002, 102(1): 57-59. doi: 10.1016/S0014-4894(02)00143-1
[10]	Egea PF. Crossing the vacuolar Rubicon: structural insights into effector protein trafficking in api complexan parasites[J]. Microorganisms, 2020, 8(6): 865. doi: 10.3390/microorganisms8060865
[11]	Sá E Cunha C,, Nyboer B,, Heiss K, et al. Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development[J]. Proc Natl Acad Sci USA, 2017, 114(7): E1138-E1147.
[12]	Elmendorf HG,, Haldar K. Plasmodium falciparum exports the Golgi marker sphingomyelin synthase into a tubovesicular network in the cytoplasm of mature erythrocytes[J]. J Cell Biol, 1994, 124(4): 449-462. pmid: 8106545
[13]	Nessel T,, Beck JM,, Rayatpisheh S, et al. EXP1 is required for organisation of EXP2 in the intraerythrocytic malaria parasite vacuole[J]. Cell Microbiol, 2020, 22(5): e13168.
[14]	Garten M,, Beck JR,, Roth R, et al. Contacting domains segregate a lipid transporter from a solute transporter in the malarial host-parasite interface[J]. Nat Commun, 2020, 11(1): 3825. doi: 10.1038/s41467-020-17506-9
[15]	Spycher C,, Rug M,, Klonis N, et al. Genesis of and trafficking to the maurer’s clefts of Plasmodium falciparum-infected erythrocytes[J]. Mol Cell Biol, 2006, 26(11): 4074-4085. doi: 10.1128/MCB.00095-06
[16]	Hanssen E,, Sougrat R,, Frankland S, et al. Electron tomography of the maurer’s cleft organelles of Plasmodium falciparum-infected erythrocytes reveals novel structural features[J]. Mol Microbiol, 2008, 67(4): 703-718. pmid: 18067543
[17]	Külzer S,, Rug M,, Brinkmann K, et al. Parasite-encoded Hsp40 proteins define novel mobile structures in the cytosol of the P. falciparum-infected erythrocyte[J]. Cell Microbiol, 2010, 12(10): 1398-1420. doi: 10.1111/j.1462-5822.2010.01477.x
[18]	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-e03319.
[19]	Matz JM,, Goosmann C,, Brinkmann V, et al. The Plasmodium berghei translocon of exported proteins reveals spatiotemporal dynamics of tubular extensions[J]. Sci Rep, 2015, 5: 12532. doi: 10.1038/srep12532
[20]	Spielmann T,, Fergusen DJP,, Beck HP. Etramps, a new Plasmodium falciparum gene family coding for developmentally regulated and highly charged membrane proteins located at the parasite-host cell interface[J]. Mol Biol Cell, 2003, 14(4): 1529-1544. doi: 10.1091/mbc.e02-04-0240 pmid: 12686607
[21]	MacKellar DC,, Vaughan AM,, Aly ASI, et al. A systematic analysis of the early transcribed membrane protein family throughout the life cycle of Plasmodium yoelii[J]. Cell Microbiol, 2011, 13(11): 1755-1767. doi: 10.1111/j.1462-5822.2011.01656.x pmid: 21819513
[22]	Lee SK,, Han JH,, Park JH, et al. Evaluation of antibody responses to the early transcribed membrane protein family in Plasmodium vivax[J]. Parasit Vectors, 2019, 12(1): 594. doi: 10.1186/s13071-019-3846-4
[23]	Saito H,, Lund-Katz S,, Phillips MC. Contributions of domain structure and lipid interaction to the functionality of exchangeable human apolipoproteins[J]. Prog Lipid Res, 2004, 43(4): 350-380. doi: 10.1016/j.plipres.2004.05.002
[24]	Vignali M,, McKinlay A,, LaCount DJ, et al. Interaction of an atypical Plasmodium falciparum ETRAMP with human apolipoproteins[J]. Malar J, 2008, 7: 211. doi: 10.1186/1475-2875-7-211
[25]	Mesén-Ramírez P,, Reinsch F,, Blancke Soares A, et al. Stable translocation intermediates jam global protein export in Plasmodium falciparum parasites and link the PTEX component EXP2 with translocation activity[J]. PLoS Pathog, 2016, 12(5): e1005618.
[26]	Vincensini L,, Richert S,, Blisnick T, et al. Proteomic analysis identifies novel proteins of the maurer’s clefts, a secretory compartment delivering Plasmodium falciparum proteins to the surface of its host cell[J]. Mol Cell Proteomics, 2005, 4(4): 582-593. doi: 10.1074/mcp.M400176-MCP200 pmid: 15671043
[27]	Currà C,, di Luca M,, Picci L, et al. The ETRAMP family member SEP2 is expressed throughout Plasmodium berghei life cycle and is released during sporozoite gliding motility[J]. PLoS One, 2013, 8(6): e67238. doi: 10.1371/journal.pone.0067238
[28]	Currà C,, Pace T,, Franke-Fayard BMD, et al. Erythrocyte remodeling in Plasmodium berghei infection: the contribution of SEP family members[J]. Traffic, 2012, 13(3): 388-399. doi: 10.1111/j.1600-0854.2011.01313.x
[29]	Andreadaki M,, Hanssen E,, Deligianni E, et al. Sequential membrane rupture and vesiculation during Plasmodium berghei gametocyte egress from the red blood cell[J]. Sci Rep, 2018, 8(1): 3543. doi: 10.1038/s41598-018-21801-3 pmid: 29476099
[30]	Venkatesh A,, Jain A,, Davies H, et al. Hospital-derived antibody profiles of malaria patients in Southwest India[J]. Malar J, 2019, 18(1): 138. doi: 10.1186/s12936-019-2771-5
[31]	Milner DA Jr,, Lee JJ,, Frantzreb C, et al. Quantitative assessment of multiorgan sequestration of parasites in fatal pediatric cerebral malaria[J]. J Infect Dis, 2015, 212(8): 1317-1321. doi: 10.1093/infdis/jiv205 pmid: 25852120
[32]	Heiber A,, Kruse F,, Pick C, et al. Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export[J]. PLoS Pathog, 2013, 9(8): e1003546.
[33]	Marti M,, Good RT,, Rug M, et al. Targeting malaria virulence and remodeling proteins to the host erythrocyte[J]. Science, 2004, 306(5703): 1930-1933. doi: 10.1126/science.1102452
[34]	Sun XD,, Zhao X,, Tu ZW, et al. Advances in the study of protein export by Plasmodium falciparum[J]. J Pathogen Biol, 2014, 9(9): 852-855. (in Chinese)
	( 孙喜东,, 赵欣,, 土志伟, 等. 恶性疟原虫蛋白输出机制的研究进展[J]. 中国病原生物学杂志, 2014, 9(9): 852-855.)
[35]	AhYoung AP,, Koehl A,, Cascio D, et al. Structural mapping of the ClpB ATPases of Plasmodium falciparum: targeting protein folding and secretion for antimalarial drug design[J]. Protein Sci, 2015, 24(9): 1508-1520. doi: 10.1002/pro.2739 pmid: 26130467
[36]	Florentin A,, Stephens DR,, Brooks CF, et al. Plastid biogenesis in malaria parasites requires the interactions and catalytic activity of the Clp proteolytic system[J]. Proc Natl Acad Sci USA, 2020, 117(24): 13719-13729. doi: 10.1073/pnas.1919501117
[37]	Hakamada K,, Watanabe H,, Kawano R, et al. Expression and characterization of the Plasmodium translocon of the exported proteins component EXP2[J]. Biochem Biophys Res Commun, 2017, 482(4): 700-705. doi: 10.1016/j.bbrc.2016.11.097
[38]	Ho CM,, Beck JR,, Lai M, et al. Malaria parasite translocon structure and mechanism of effector export[J]. Nature, 2018, 561(7721): 70-75. doi: 10.1038/s41586-018-0469-4
[39]	Chisholm SA,, Kalanon M,, Nebl T, et al. The malaria PTEX component PTEX88 interacts most closely with HSP101 at the host-parasite interface[J]. FEBS J, 2018, 285(11): 2037-2055. doi: 10.1111/febs.14463 pmid: 29637707
[40]	Matthews K,, Kalanon M,, Chisholm SA, et al. The Plasmodium translocon of exported proteins (PTEX) component thioredoxin-2 is important for maintaining normal blood-stage growth[J]. Mol Microbiol, 2013, 89(6): 1167-1186. doi: 10.1111/mmi.12334 pmid: 23869529
[41]	Chisholm SA,, McHugh E,, Lundie R, et al. Contrasting inducible knockdown of the auxiliary PTEX component PTEX88 in P. falciparum and P. berghei unmasks a role in parasite virulence[J]. PLoS One, 2016, 11(2): e0149296.
[42]	Peng M,, Cascio D,, Egea PF. Crystal structure and solution characterization of the thioredoxin-2 from Plasmodium falciparum, a constituent of an essential parasitic protein export complex[J]. Biochem Biophys Res Commun, 2015, 456(1): 403-409. doi: 10.1016/j.bbrc.2014.11.096
[43]	Elsworth B,, Sanders PR,, Nebl T, et al. Proteomic analysis reveals novel proteins associated with the Plasmodium protein exporter PTEX and a loss of complex stability upon truncation of the core PTEX component, PTEX150[J]. Cell Microbiol, 2016, 18(11): 1551-1569. doi: 10.1111/cmi.12596 pmid: 27019089
[44]	Low LM,, Azasi Y,, Sherling ES, et al. Deletion of Plasmodium falciparum protein RON3 affects the functional translocation of exported proteins and glucose uptake[J]. mBio, 2019, 10(4): e01460-e01419.
[45]	Morita M,, Nagaoka H,, Ntege EH, et al. PV1, a novel Plasmodium falciparum merozoite dense granule protein, interacts with exported protein in infected erythrocytes[J]. Sci Rep, 2018, 8(1): 3696. doi: 10.1038/s41598-018-22026-0
[46]	Gold DA,, Kaplan AD,, LIS A, et al. The Toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole[J]. Cell Host Microbe, 2015, 17(5): 642-652. doi: 10.1016/j.chom.2015.04.003
[47]	Garten M,, Nasamu AS,, Niles JC, et al. EXP2 is a nutrient-permeable channel in the vacuolar membrane of Plasmodium and is essential for protein export via PTEX[J]. Nat Microbiol, 2018, 3(10): 1090-1098. doi: 10.1038/s41564-018-0222-7
[48]	Mesén-Ramírez P,, Bergmann B,, Tran TT, et al. EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites[J]. PLoS Biol, 2019, 17(9): e3000473.
[49]	Pal C,, Kundu MK,, Bandyopadhyay U, et al. Synthesis of novel heme-interacting acridone derivatives to prevent free heme-mediated protein oxidation and degradation[J]. Bioorg Med Chem Lett, 2011, 21(12): 3563-3567. doi: 10.1016/j.bmcl.2011.04.127
[50]	Saha SJ,, Siddiqui AA,, Pramanik S, et al. Hydrazonophenol, a food vacuole-targeted and ferriprotoporphyrin IX-interacting chemotype prevents drug-resistant malaria[J]. ACS Infect Dis, 2019, 5(1): 63-73. doi: 10.1021/acsinfecdis.8b00178
[51]	Iriko H,, Ishino T,, Otsuki H, et al. Plasmodium falciparum exported protein 1 is localized to dense granules in merozoites[J]. Parasitol Int, 2018, 67(5): 637-639. doi: 10.1016/j.parint.2018.06.001
[52]	Lisewski AM,, Quiros JP,, Ng CL, et al. Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate[J]. Cell, 2014, 158(4): 916-928. doi: S0092-8674(14)00925-8 pmid: 25126794
[53]	Cooper RA,, Papakrivos J,, Lane KD, et al. PfCG2, a Plasmodium falciparum protein peripherally associated with the parasitophorous vacuolar membrane, is expressed in the period of maximum hemoglobin uptake and digestion by trophozoites[J]. Mol Biochem Parasitol, 2005, 144(2): 167-176. doi: 10.1016/j.molbiopara.2005.07.009
[54]	Wicht KJ,, Mok S,, Fidock DA. Molecular mechanisms of drug resistance in Plasmodium falciparum malaria[J]. Annu Rev Microbiol, 2020, 74: 431-454. doi: 10.1146/annurev-micro-020518-115546
[55]	Yang B,, Sun YF,, Lei Y, et al. Research progress on the treatment of malaria with artemisinin and its derivatives[J]. Chin J Parasitol Parasit Dis, 2021, 39(3): 393-402. (in Chinese)
	( 杨博,, 孙毅凡,, 雷瑶, 等. 青蒿素及其衍生物治疗疟疾的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(3): 393-402.)
[56]	Li J,, Wu LO,, Yang ZQ. Comparison of efficacy of artemisinin antimalarials and combined use the drugs[J]. Chin Trop Med, 2009, 9(1): 157-159, 195. (in Chinese)
	( 李佳,, 吴兰鸥,, 杨照青. 青蒿素类抗疟药药效的比较及联合用药[J]. 中国热带医学, 2009, 9(1): 157-159, 195.)
[57]	Boddey JA,, Cowman AF. Plasmodium nesting: remaking the erythrocyte from the inside out[J]. Annu Rev Microbiol, 2013, 67: 243-269. doi: 10.1146/annurev-micro-092412-155730
[58]	Hiller NL,, Akompong T,, Morrow JS, et al. Identification of a stomatin orthologue in vacuoles induced in human erythrocytes by malaria parasites: a role for microbial raft proteins in api complexan vacuole biogenesis[J]. J Biol Chem, 2003, 278(48): 48413-48421. doi: 10.1074/jbc.M307266200 pmid: 12968029
[59]	Counihan NA,, Chisholm SA,, Bullen HE, et al. Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate[J]. eLife, 2017, 6: e23217. doi: 10.7554/eLife.23217
[60]	Gupta A,, Thiruvengadam G,, Desai SA. The conserved clag multigene family of malaria parasites: essential roles in host-pathogen interaction[J]. Drug Resist Updat, 2015, 18: 47-54. doi: 10.1016/j.drup.2014.10.004
[61]	Comeaux CA,, Coleman BI,, Bei AK, et al. Functional analysis of epigenetic regulation of tandem RhopH1/clag genes reveals a role in Plasmodium falciparum growth[J]. Mol Microbiol, 2011, 80(2): 378-390. doi: 10.1111/j.1365-2958.2011.07572.x
[62]	Parish LA,, Mai DW,, Jones ML, et al. A member of the Plasmodium falciparum PHIST family binds to the erythrocyte cytoskeleton component band 4.1[J]. Malar J, 2013, 12: 160. doi: 10.1186/1475-2875-12-160
[63]	Shakya B,, Penn WD,, Nakayasu ES, et al. The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1[J]. Mol Biochem Parasitol, 2017, 216: 5-13. doi: 10.1016/j.molbiopara.2017.06.002
[64]	Thieleke-Matos C,, Lopes da Silva M,, Cabrita-Santos L, et al. Host cell autophagy contributes to Plasmodium liver development[J]. Cell Microbiol, 2016, 18(3): 437-450. doi: 10.1111/cmi.12524 pmid: 26399761
[65]	Wolanin K,, Fontinha D,, Sanches-Vaz M, et al. A crucial role for the C-terminal domain of exported protein 1 during the mosquito and hepatic stages of the Plasmodium berghei life cycle[J]. Cell Microbiol, 2019, 21(10): e13088.
[66]	Mikolajczak SA,, Jacobs-Lorena V,, MacKellar DC, et al. L-FABP is a critical host factor for successful malaria liver stage development[J]. Int J Parasitol, 2007, 37(5): 483-489. pmid: 17303141
[67]	Real E,, Rodrigues L,, Cabal GG, et al. Plasmodium UIS3 sequesters host LC3 to avoid elimination by autophagy in hepatocytes[J]. Nat Microbiol, 2018, 3(1): 17-25. doi: 10.1038/s41564-017-0054-x
[68]	Lu F,, Zhuo XH,, Lu SH, et al. Research progress on the interaction between host cell autophagy and apicomplexa protozoa infection[J/OL]. Chin J Parasitol Parasit Dis: 1-6[2022-01-11]. http://kns.cnki.net/kcms/detail/31.1248.R.20211213.0856.002.html. (in Chinese)
	( 鲁飞,, 卓洵辉,, 陆绍红. 顶复门原虫感染与宿主细胞自噬相互作用的研究进展[J/OL]. 中国寄生虫学与寄生虫病杂志: 1-6[2022-01-11]. http://kns.cnki.net/kcms/detail/31.1248.R.20211213.0856.002.html. )
[69]	Burda PC,, Roelli MA,, Schaffner M, et al. A Plasmodium phospholipase is involved in disruption of the liver stage parasitophorous vacuole membrane[J]. PLoS Pathog, 2015, 11(3): e1004760.
[70]	de Niz M,, Caldelari R,, Kaiser G, et al. Hijacking of the host cell Golgi by Plasmodium berghei liver stage parasites[J]. J Cell Sci, 2021, 134(10): jcs252213.
[71]	Ross A,, Koepfli C,, Schoepflin S, et al. The incidence and differential seasonal patterns of Plasmodium vivax primary infections and relapses in a cohort of children in Papua new Guinea[J]. PLoS Negl Trop Dis, 2016, 10(5): e0004582.
[72]	Schafer C,, Dambrauskas N,, Steel RW, et al. A recombinant antibody against Plasmodium vivax UIS4 for distinguishing replicating from dormant liver stages[J]. Malar J, 2018, 17(1): 370. doi: 10.1186/s12936-018-2519-7
[73]	Chawla J,, Oberstaller J,, Adams JH. Targeting gametocytes of the malaria parasite Plasmodium falciparum in a functional genomics era: next steps[J]. Pathogens, 2021, 10(3): 346. doi: 10.3390/pathogens10030346
[74]	Baker DA,, Daramola O,, McCrossan MV, et al. Subcellular localization of Pfs16, a Plasmodium falciparum gametocyte antigen[J]. Parasitology, 1994, 108 (Pt 2): 129-137. doi: 10.1017/S0031182000068219
[75]	Kongkasuriyachai D,, Fujioka H,, Kumar N. Functional analysis of Plasmodium falciparum parasitophorous vacuole membrane protein (Pfs16) during gametocytogenesis and gametogenesis by targeted gene disruption[J]. Mol Biochem Parasitol, 2004, 133(2): 275-285. doi: 10.1016/j.molbiopara.2003.10.014
[76]	Deligianni E,, Andreadaki M,, Koutsouris K, et al. Sequence and functional divergence of gametocyte-specific parasitophorous vacuole membrane proteins in Plasmodium parasites[J]. Mol Biochem Parasitol, 2018, 220: 15-18. doi: 10.1016/j.molbiopara.2018.01.002
[77]	Lanfrancotti A,, Bertuccini L,, Silvestrini F, et al. Plasmodium falciparum: MRNA co-expression and protein co-localisation of two gene products upregulated in early gametocytes[J]. Exp Parasitol, 2007, 116(4): 497-503. pmid: 17367781
[78]	Furuya T,, Mu JB,, Hayton K, et al. Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis[J]. Proc Natl Acad Sci USA, 2005, 102(46): 16813-16818. doi: 10.1073/pnas.0501858102
[79]	Janse CJ,, Haghparast A,, Speranca MA, et al. Malaria parasites lacking eef1a have a normal S/M phase yet grow more slowly due to a longer G1 phase[J]. Mol Microbiol, 2003, 50(5): 1539-1551. doi: 10.1046/j.1365-2958.2003.03820.x
[80]	Ponzi M,, Sidén-Kiamos I,, Bertuccini L, et al. Egress of Plasmodium berghei gametes from their host erythrocyte is mediated by the MDV-1/PEG3 protein[J]. Cell Microbiol, 2009, 11(8): 1272-1288. doi: 10.1111/j.1462-5822.2009.01331.x
[81]	Schnider CB,, Bausch-Fluck D,, Brühlmann F, et al. BioID reveals novel proteins of the Plasmodium parasitophorous vacuole membrane[J]. mSphere, 2018, 3(1): e00522-e00517.