Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
권호 표지
DOI QR코드

DOI QR Code

Identification of Immunodominant B-cell Epitope Regions of Reticulocyte Binding Proteins in Plasmodium vivax by Protein Microarray Based Immunoscreening

  • Han, Jin-Hee (Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University) ;
  • Li, Jian (Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University) ;
  • Wang, Bo (Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University) ;
  • Lee, Seong-Kyun (Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University) ;
  • Nyunt, Myat Htut (Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University) ;
  • Na, Sunghun (Department of Obstetrics and Gynecology School of Medicine, Kangwon National University) ;
  • Park, Jeong-Hyun (Department of Anatomy, School of Medicine, Kangwon National University) ;
  • Han, Eun-Taek (Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University)
  • Received : 2015.02.28
  • Accepted : 2015.07.23
  • Published : 2015.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Plasmodium falciparum can invade all stages of red blood cells, while Plasmodium vivax can invade only reticulocytes. Although many P. vivax proteins have been discovered, their functions are largely unknown. Among them, P. vivax reticulocyte binding proteins (PvRBP1 and PvRBP2) recognize and bind to reticulocytes. Both proteins possess a C-terminal hydrophobic transmembrane domain, which drives adhesion to reticulocytes. PvRBP1 and PvRBP2 are large (>326 kDa), which hinders identification of the functional domains. In this study, the complete genome information of the P. vivax RBP family was thoroughly analyzed using a prediction server with bioinformatics data to predict B-cell epitope domains. Eleven pvrbp family genes that included 2 pseudogenes and 9 full or partial length genes were selected and used to express recombinant proteins in a wheat germ cell-free system. The expressed proteins were used to evaluate the humoral immune response with vivax malaria patients and healthy individual serum samples by protein microarray. The recombinant fragments of 9 PvRBP proteins were successfully expressed; the soluble proteins ranged in molecular weight from 16 to 34 kDa. Evaluation of the humoral immune response to each recombinant PvRBP protein indicated a high antigenicity, with 38-88% sensitivity and 100% specificity. Of them, N-terminal parts of PvRBP2c (PVX_090325-1) and PvRBP2 like partial A (PVX_090330-1) elicited high antigenicity. In addition, the PvRBP2-like homologue B (PVX_116930) fragment was newly identified as high antigenicity and may be exploited as a potential antigenic candidate among the PvRBP family. The functional activity of the PvRBP family on merozoite invasion remains unknown.

Keywords

References

  1. World Health Organization. World Malaria Report (2014). 2014.
  2. Gething PW, Elyazar IR, Moyes CL, Smith DL, Battle KE, Guerra CA, Patil AP, Tatem AJ, Howes RE, Myers MF, George DB, Horby P, Wertheim HF, Price RN, Mueller I, Baird JK, Hay SI. A long neglected world malaria map: Plasmodium vivax endemicity in 2010. PLoS Negl Trop Dis 2012; 6: e1814. https://doi.org/10.1371/journal.pntd.0001814
  3. Birkett AJ, Moorthy VS, Loucq C, Chitnis CE, Kaslow DC. Malaria vaccine R&D in the Decade of Vaccines: breakthroughs, challenges and opportunities. Vaccine 2013; 31 (suppl 2): B233-B243. https://doi.org/10.1016/j.vaccine.2013.02.040
  4. Noulin F, Borlon C, Van Den Abbeele J, D'Alessandro U, Erhart A. 1912-2012: a century of research on Plasmodium vivax in vitro culture. Trends Parasitol 2013; 29: 286-294. https://doi.org/10.1016/j.pt.2013.03.012
  5. Udomsangpetch R, Kaneko O, Chotivanich K, Sattabongkot J. Cultivation of Plasmodium vivax. Trends Parasitol 2008; 24: 85-88. https://doi.org/10.1016/j.pt.2007.09.010
  6. Ubaida Mohien C, Colquhoun DR, Mathias DK, Gibbons JG, Armistead JS, Rodriguez MC, Rodriguez MH, Edwards NJ, Hartler J, Thallinger GG, Graham DR, Martinez-Barnetche J, Rokas A, Dinglasan RR. A bioinformatics approach for integrated transcriptomic and proteomic comparative analyses of model and non-sequenced anopheline vectors of human malaria parasites. Mol Cell Proteomics 2013; 12: 120-131. https://doi.org/10.1074/mcp.M112.019596
  7. Fard AT, Salman A, Kazemi B, Bokhari H. In silico comparative genome analysis of malaria parasite Plasmodium falciparum and Plasmodium vivax chromosome 4. Parasitol Res 2009; 104: 1361-1364. https://doi.org/10.1007/s00436-009-1338-8
  8. Jones ML, Kitson EL, Rayner JC. Plasmodium falciparum erythrocyte invasion: a conserved myosin associated complex. Mol Biochem Parasitol 2006; 147: 74-84. https://doi.org/10.1016/j.molbiopara.2006.01.009
  9. Keeley A, Soldati D. The glideosome: a molecular machine powering motility and host-cell invasion by Apicomplexa. Trends Cell Biol 2004; 14: 528-532. https://doi.org/10.1016/j.tcb.2004.08.002
  10. Cowman AF, Crabb BS. Invasion of red blood cells by malaria parasites. Cell 2006; 124: 755-766. https://doi.org/10.1016/j.cell.2006.02.006
  11. Wright GJ, Rayner JC. Plasmodium falciparum erythrocyte invasion: combining function with immune evasion. PLoS Pathog 2014; 10: e1003943. https://doi.org/10.1371/journal.ppat.1003943
  12. Cowman AF, Berry D, Baum J. The cellular and molecular basis for malaria parasite invasion of the human red blood cell. J Cell Biol 2012; 198: 961-971. https://doi.org/10.1083/jcb.201206112
  13. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 2002; 419: 498-511. https://doi.org/10.1038/nature01097
  14. Carlton JM, Adams JH, Silva JC, Bidwell SL, Lorenzi H, Caler E, Crabtree J, Angiuoli SV, Merino EF, Amedeo P, Cheng Q, Coulson RM, Crabb BS, Del Portillo HA, Essien K, Feldblyum TV, Fernandez-Becerra C, Gilson PR, Gueye AH, Guo X, Kang'a S, Kooij TW, Korsinczky M, Meyer EV, Nene V, Paulsen I, White O, Ralph SA, Ren Q, Sargeant TJ, Salzberg SL, Stoeckert CJ, Sullivan SA, Yamamoto MM, Hoffman SL, Wortman JR, Gardner MJ, Galinski MR, Barnwell JW, Fraser-Liggett CM. Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature 2008; 455: 757-763. https://doi.org/10.1038/nature07327
  15. Kappe SH, Noe AR, Fraser TS, Blair PL, Adams JH. A family of chimeric erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci USA 1998; 95: 1230-1235. https://doi.org/10.1073/pnas.95.3.1230
  16. Adams JH, Sim BK, Dolan SA, Fang X, Kaslow DC, Miller LH. A family of erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci USA 1992; 89: 7085-7089. https://doi.org/10.1073/pnas.89.15.7085
  17. Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ, Miller LH. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science 1993; 261: 1182-1184. https://doi.org/10.1126/science.7689250
  18. Menard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR, Ratsimbasoa A, Thonier V, Carod JF, Domarle O, Colin Y, Bertrand O, Picot J, King CL, Grimberg BT, Mercereau-Puijalon O, Zimmerman PA. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA 2010; 107: 5967-5971. https://doi.org/10.1073/pnas.0912496107
  19. Galinski MR, Medina CC, Ingravallo P, Barnwell JW. A reticulocyte-binding protein complex of Plasmodium vivax merozoites. Cell 1992; 69: 1213-1226. https://doi.org/10.1016/0092-8674(92)90642-P
  20. Miller LH, Baruch DI, Marsh K, Doumbo OK. The pathogenic basis of malaria. Nature 2002; 415: 673-679. https://doi.org/10.1038/415673a
  21. Kosaisavee V, Lek-Uthai U, Suwanarusk R, Gruner AC, Russell B, Nosten F, Renia L, Snounou G. Genetic diversity in new members of the reticulocyte binding protein family in Thai Plasmodium vivax isolates. PLoS One 2012; 7: e32105. https://doi.org/10.1371/journal.pone.0032105
  22. Li J, Han ET. Dissection of the Plasmodium vivax reticulocyte binding-like proteins (PvRBPs). Biochem Biophys Res Commun 2012; 426: 1-6. https://doi.org/10.1016/j.bbrc.2012.08.055
  23. Bozdech Z, Mok S, Hu G, Imwong M, Jaidee A, Russell B, Ginsburg H, Nosten F, Day NP, White NJ, Carlton JM, Preiser PR. The transcriptome of Plasmodium vivax reveals divergence and diversity of transcriptional regulation in malaria parasites. Proc Natl Acad Sci USA 2008; 105: 16290-16295. https://doi.org/10.1073/pnas.0807404105
  24. List C, Qi W, Maag E, Gottstein B, Muller N, Felger I. Serodiagnosis of Echinococcus spp. infection: explorative selection of diagnostic antigens by peptide microarray. PLoS Negl Trop Dis 2010; 4: e771. https://doi.org/10.1371/journal.pntd.0000771
  25. Noya O, Patarroyo ME, Guzman F, Alarcon de Noya B. Immunodiagnosis of parasitic diseases with synthetic peptides. Curr Protein Pept Sci 2003; 4: 299-308. https://doi.org/10.2174/1389203033487153
  26. Assis LM, Sousa JR, Pinto NF, Silva AA, Vaz AF, Andrade PP, Carvalho EM, De Melo MA. B-cell epitopes of antigenic proteins in Leishmania infantum: an in silico analysis. Parasite Immunol 2014; 36: 313-323. https://doi.org/10.1111/pim.12111
  27. Singh H, Ansari HR, Raghava GP. Improved method for linear B-cell epitope prediction using antigen's primary sequence. PLoS One 2013; 8: e62216. https://doi.org/10.1371/journal.pone.0062216
  28. Saha S, Raghava GPS. BcePred: Prediction of continuous B-cell epitopes in antigenic sequences using physico-chemical properties. Artificial Immune Systems, Proceedings 2004; 3239: 197-204.
  29. Saha S, Raghava GP. Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins 2006; 65: 40-48. https://doi.org/10.1002/prot.21078
  30. Larsen JE, Lund O, Nielsen M. Improved method for predicting linear B-cell epitopes. Immunome Res 2006; 2: 2. https://doi.org/10.1186/1745-7580-2-2
  31. Yang X, Yu X. An introduction to epitope prediction methods and software. Rev Med Virol 2009; 19: 77-96. https://doi.org/10.1002/rmv.602
  32. Mahdavi M, Mohabatkar H, Keyhanfar M, Dehkordi AJ, Rabbani M. Linear and conformational B cell epitope prediction of the HER 2 ECD-subdomain III by in silico methods. Asian Pac J Cancer Prev 2012; 13: 3053-3059. https://doi.org/10.7314/APJCP.2012.13.7.3053
  33. Bouillon A, Giganti D, Benedet C, Gorgette O, Petres S, Crublet E, Girard-Blanc C, Witkowski B, Menard D, Nilges M, Mercereau-Puijalon O, Stoven V, Barale JC. In Silico screening on the three-dimensional model of the Plasmodium vivax SUB1 protease leads to the validation of a novel anti-parasite compound. J Biol Chem 2013; 288: 18561-18573. https://doi.org/10.1074/jbc.M113.456764
  34. Restrepo-Montoya D, Becerra D, Carvajal-Patino JG, Mongui A, Nino LF, Patarroyo ME, Patarroyo MA. Identification of Plasmodium vivax proteins with potential role in invasion using sequence redundancy reduction and profile hidden Markov models. PLoS One 2011; 6: e25189. https://doi.org/10.1371/journal.pone.0025189
  35. Cheng Y, Wang Y, Ito D, Kong DH, Ha KS, Chen JH, Lu F, Li J, Wang B, Takashima E, Sattabongkot J, Tsuboi T, Han ET. The Plasmodium vivax merozoite surface protein 1 paralog is a novel erythrocyte-binding ligand of P. vivax. Infect Immun 2013; 81: 1585-1595. https://doi.org/10.1128/IAI.01117-12
  36. Cespedes N, Habel C, Lopez-Perez M, Castellanos A, Kajava AV, Servis C, Felger I, Moret R, Arevalo-Herrera M, Corradin G, Herrera S. Plasmodium vivax antigen discovery based on alpha-helical coiled coil protein motif. PLoS One 2014; 9: e100440. https://doi.org/10.1371/journal.pone.0100440
  37. Crowther GJ, Shanmugam D, Carmona SJ, Doyle MA, Hertz-Fowler C, Berriman M, Nwaka S, Ralph SA, Roos DS, Van Voorhis WC, Aguero F. Identification of attractive drug targets in neglected-disease pathogens using an in silico approach. PLoS Negl Trop Dis 2010; 4: e804. https://doi.org/10.1371/journal.pntd.0000804
  38. Kulangara C, Kajava AV, Corradin G, Felger I. Sequence conservation in Plasmodium falciparum alpha-helical coiled coil domains proposed for vaccine development. PLoS One 2009; 4: e5419. https://doi.org/10.1371/journal.pone.0005419
  39. Olugbile S, Villard V, Bertholet S, Jafarshad A, Kulangara C, Roussilhon C, Frank G, Agak GW, Felger I, Nebie I, Konate K, Kajava AV, Schuck P, Druilhe P, Spertini F, Corradin G. Malaria vaccine candidate: design of a multivalent subunit alpha-helical coiled coil poly-epitope. Vaccine 2011; 29: 7090-7099. https://doi.org/10.1016/j.vaccine.2011.06.122
  40. Neafsey DE, Galinsky K, Jiang RH, Young L, Sykes SM, Saif S, Gujja S, Goldberg JM, Young S, Zeng Q, Chapman SB, Dash AP, Anvikar AR, Sutton PL, Birren BW, Escalante AA, Barnwell JW, Carlton JM. The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum. Nat Genet 2012; 44: 1046-1050. https://doi.org/10.1038/ng.2373
  41. Bowman S, Lawson D, Basham D, Brown D, Chillingworth T, Churcher CM, Craig A, Davies RM, Devlin K, Feltwell T, Gentles S, Gwilliam R, Hamlin N, Harris D, Holroyd S, Hornsby T, Horrocks P, Jagels K, Jassal B, Kyes S, McLean J, Moule S, Mungall K, Murphy L, Oliver K, Quail MA, Rajandream MA, Rutter S, Skelton J, Squares R, Squares S, Sulston JE, Whitehead S, Woodward JR, Newbold C, Barrell BG. The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature 1999; 400: 532-538. https://doi.org/10.1038/22964
  42. Hall N, Pain A, Berriman M, Churcher C, Harris B, Harris D, Mungall K, Bowman S, Atkin R, Baker S, Barron A, Brooks K, Buckee CO, Burrows C, Cherevach I, Chillingworth C, Chillingworth T, Christodoulou Z, Clark L, Clark R, Corton C, Cronin A, Davies R, Davis P, Dear P, Dearden F, Doggett J, Feltwell T, Goble A, Goodhead I, Gwilliam R, Hamlin N, Hance Z, Harper D, Hauser H, Hornsby T, Holroyd S, Horrocks P, Humphray S, Jagels K, James KD, Johnson D, Kerhornou A, Knights A, Konfortov B, Kyes S, Larke N, Lawson D, Lennard N, Line A, Maddison M, McLean J, Mooney P, Moule S, Murphy L, Oliver K, Ormond D, Price C, Quail MA, Rabbinowitsch E, Rajandream MA, Rutter S, Rutherford KM, Sanders M, Simmonds M, Seeger K, Sharp S, Smith R, Squares R, Squares S, Stevens K, Taylor K, Tivey A, Unwin L, Whitehead S, Woodward J, Sulston JE, Craig A, Newbold C, Barrell BG. Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Nature 2002; 419: 527-531. https://doi.org/10.1038/nature01095
  43. Villard V, Agak GW, Frank G, Jafarshad A, Servis C, Nebie I, Sirima SB, Felger I, Arevalo-Herrera M, Herrera S, Heitz F, Backer V, Druilhe P, Kajava AV, Corradin G. Rapid identification of malaria vaccine candidates based on alpha-helical coiled coil protein motif. PLoS One 2007; 2: e645. https://doi.org/10.1371/journal.pone.0000645
  44. Tran TM, Oliveira-Ferreira J, Moreno A, Santos F, Yazdani SS, Chitnis CE, Altman JD, Meyer EV, Barnwell JW, Galinski MR. Comparison of IgG reactivities to Plasmodium vivax merozoite invasion antigens in a Brazilian Amazon population. Am J Trop Med Hyg 2005; 73: 244-255.
  45. Rayner JC, Tran TM, Corredor V, Huber CS, Barnwell JW, Galinski MR. Dramatic difference in diversity between Plasmodium falciparum and Plasmodium vivax reticulocyte binding-like genes. Am J Trop Med Hyg 2005; 72: 666-674.
  46. Prajapati SK, Kumari P, Singh OP. Molecular analysis of reticulocyte binding protein-2 gene in Plasmodium vivax isolates from India. BMC Microbiol 2012; 12: 243. https://doi.org/10.1186/1471-2180-12-243

Cited by

  1. Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children vol.10, pp.9, 2016, https://doi.org/10.1371/journal.pntd.0005014
  2. Identification of a reticulocyte-specific binding domain of Plasmodium vivax reticulocyte-binding protein 1 that is homologous to the PfRh4 erythrocyte-binding domain vol.6, pp.None, 2015, https://doi.org/10.1038/srep26993
  3. Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA) binds human erythrocytes independent of Duffy antigen status vol.6, pp.None, 2016, https://doi.org/10.1038/srep35581
  4. Gene Models, Expression Repertoire, and Immune Response of Plasmodium vivax Reticulocyte Binding Proteins vol.84, pp.3, 2016, https://doi.org/10.1128/iai.01117-15
  5. What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates? vol.8, pp.None, 2015, https://doi.org/10.3389/fimmu.2017.00126
  6. Identification and Immunological Characterization of the Ligand Domain of Plasmodium vivax Reticulocyte Binding Protein 1a vol.218, pp.7, 2018, https://doi.org/10.1093/infdis/jiy273
  7. Contribution of Plasmodium immunomics: potential impact for serological testing and surveillance of malaria vol.16, pp.2, 2015, https://doi.org/10.1080/14789450.2019.1554441
  8. From a basic to a functional approach for developing a blood stage vaccine against Plasmodium vivax vol.19, pp.2, 2020, https://doi.org/10.1080/14760584.2020.1733421
  9. Epitope-Based Vaccine Designing of Nocardia asteroides Targeting the Virulence Factor Mce-Family Protein by Immunoinformatics Approach vol.26, pp.2, 2015, https://doi.org/10.1007/s10989-019-09921-4
  10. Prediction of B cell and T‐helper cell epitopes candidates of bovine leukaemia virus (BLV) by in silico approach vol.6, pp.4, 2015, https://doi.org/10.1002/vms3.307