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Identification and characterization of the Plasmodium falciparum RhopH2 ortholog in Plasmodium vivax

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Abstract

Plasmodium vivax is one of the most important human malaria species that is geographically widely endemic and potentially affects a larger number of people than its more notorious cousin, Plasmodium falciparum. During invasion of red blood cells, the parasite requires the intervention of high molecular weight complex rhoptry proteins (RhopH) that are also essential for cytoadherence. PfRhopH2, a member of the RhopH multigene family, has been characterized as being crucial during P. falciparum infection. This study describes identifying and characterizing the pfrhoph2 orthologous gene in P. vivax (hereinafter named pvrhoph2). The PvRhopH2 is a 1,369-amino acid polypeptide encoded by PVX_099930 gene, for which orthologous genes have been identified in other Plasmodium species by bioinformatic approaches. Both P. falciparum and P. vivax genes contain nine introns, and there is a high degree of similarity between the deduced amino acid sequences of the two proteins. Moreover, PvRhopH2 contains a signal peptide at its N-terminus and 12 cysteines predominantly in its C-terminal half. PvRhopH2 is localized in one of the apical organelles of the merozoite, the rhoptry, and the localization pattern is similar to that of PfRhopH2 in P. falciparum. The recombinant PvRhopH2 protein is recognized by serum antibodies of patients naturally exposed to P. vivax, suggesting that PvRhopH2 is immunogenic in humans.

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References

  • Anthony RN, Yang J, Krall JA, Sam-Yellowe TY (2000) Sequence analysis of the Rhop-3 gene of Plasmodium yoelii. J Eukaryot Microbiol 47(3):319–322

    Article  PubMed  CAS  Google Scholar 

  • Beeson JG, Osier FH, Engwerda CR (2008) Recent insights into humoral and cellular immune responses against malaria. Trends Parasitol 24(12):578–584

    Article  PubMed  CAS  Google Scholar 

  • Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340(4):783–795. doi:10.1016/j.jmb.2004.05.028S0022283604005972

    Article  PubMed  Google Scholar 

  • Blisnick T, Morales Betoulle ME, Barale JC, Uzureau P, Berry L, Desroses S, Fujioka H, Mattei D, Braun Breton C (2000) Pfsbp1, a Maurer’s cleft Plasmodium falciparum protein, is associated with the erythrocyte skeleton. Mol Biochem Parasitol 111(1):107–121

    Article  PubMed  CAS  Google Scholar 

  • Brown HJ, Coppel RL (1991) Primary structure of a Plasmodium falciparum rhoptry antigen. Mol Biochem Parasitol 49(1):99–110

    Article  PubMed  CAS  Google Scholar 

  • Campbell GH, Miller LH, Hudson D, Franco EL, Andrysiak PM (1984) Monoclonal antibody characterization of Plasmodium falciparum antigens. AmJTrop Med Hyg 33(6):1051–1054

    CAS  Google Scholar 

  • 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 (2008) Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature 455(7214):757–763

    Article  PubMed  CAS  Google Scholar 

  • Chen JH, Jung JW, Wang Y, Ha KS, Lu F, Lim CS, Takeo S, Tsuboi T, Han ET (2010) Immunoproteomics profiling of blood stage Plasmodium vivax infection by high-throughput screening assays. J Proteome Res 9(12):6479–6489. doi:10.1021/pr100705g

    Article  PubMed  CAS  Google Scholar 

  • Chen JH, Wang Y, Ha KS, Lu F, Suh IB, Lim CS, Park JH, Takeo S, Tsuboi T, Han ET (2011) Measurement of naturally acquired humoral immune responses against the C-terminal region of the Plasmodium vivax MSP1 protein using protein arrays. Parasitol Res 109(5):1259–1266. doi:10.1007/s00436-011-2370-z

    Article  PubMed  Google Scholar 

  • Coppel RL, Bianco AE, Culvenor JG, Crewther PE, Brown GV, Anders RF, Kemp DJ (1987) A cDNA clone expressing a rhoptry protein of Plasmodium falciparum. Mol Biochem Parasitol 25(1):73–81

    Article  PubMed  CAS  Google Scholar 

  • Jagannadham MV, Abou-Eladab EF, Kulkarni HM (2011) Identification of outer membrane proteins from an Antarctic bacterium Pseudomonas syringae Lz4W. Mol Cell Proteomics 10(6):M110 004549

    PubMed  Google Scholar 

  • Kaneko O (2007) Erythrocyte invasion: vocabulary and grammar of the Plasmodium rhoptry. Parasitol Int 56(4):255–262

    Article  PubMed  CAS  Google Scholar 

  • Kaneko O, Tsuboi T, Ling IT, Howell S, Shirano M, Tachibana M, Cao YM, Holder AA, Torii M (2001) The high molecular mass rhoptry protein, RhopH1, is encoded by members of the clag multigene family in Plasmodium falciparum and Plasmodium yoelii. Mol Biochem Parasitol 118(2):223–231

    Article  PubMed  CAS  Google Scholar 

  • Kats LM, Cooke BM, Coppel RL, Black CG (2008) Protein trafficking to apical organelles of malaria parasites—building an invasion machine. Traffic 9(2):176–186

    Article  PubMed  CAS  Google Scholar 

  • Li J, Ito D, Chen JH, Lu F, Cheng Y, Wang B, Ha KS, Cao J, Torii M, Sattabongkot J, Tsuboi T, Han ET (2012) Pv12, a 6-Cys antigen of Plasmodium vivax, is localized to the merozoite rhoptry. Parasitol Int 61(3):443–449

    Article  PubMed  CAS  Google Scholar 

  • Ling IT, Kaneko O, Narum DL, Tsuboi T, Howell S, Taylor HM, Scott-Finnigan TJ, Torii M, Holder AA (2003) Characterisation of the rhoph2 gene of Plasmodium falciparum and Plasmodium yoelii. Mol Biochem Parasitol 127(1):47–57

    Article  PubMed  CAS  Google Scholar 

  • Ling IT, Florens L, Dluzewski AR, Kaneko O, Grainger M, Yim Lim BY, Tsuboi T, Hopkins JM, Johnson JR, Torii M, Bannister LH, Yates JR 3rd, Holder AA, Mattei D (2004) The Plasmodium falciparum clag9 gene encodes a rhoptry protein that is transferred to the host erythrocyte upon invasion. Mol Microbiol 52(1):107–118. doi:10.1111/j.1365-2958.2003.03969.xMMI3969

    Article  PubMed  CAS  Google Scholar 

  • Lustigman S, Anders RF, Brown GV, Coppel RL (1988) A component of an antigenic rhoptry complex of Plasmodium falciparum is modified after merozoite invasion. Mol Biochem Parasitol 30(3):217–224

    Article  PubMed  CAS  Google Scholar 

  • Mongui A, Perez-Leal O, Rojas-Caraballo J, Angel DI, Cortes J, Patarroyo MA (2007) Identifying and characterising the Plasmodium falciparum RhopH3 Plasmodium vivax homologue. Biochem Biophys Res Commun 358(3):861–866

    Article  PubMed  CAS  Google Scholar 

  • Moreno-Perez DA, Mongui A, Soler LN, Sanchez-Ladino M, Patarroyo MA (2011) Identifying and characterizing a member of the RhopH1/Clag family in Plasmodium vivax. Gene 481(1):17–23

    Article  PubMed  CAS  Google Scholar 

  • Persson KE, Lee CT, Marsh K, Beeson JG (2006) Development and optimization of high-throughput methods to measure Plasmodium falciparum-specific growth inhibitory antibodies. J Clin Microbiol 44(5):1665–1673

    Article  PubMed  CAS  Google Scholar 

  • Pinzon CG, Curtidor H, Garcia J, Vanegas M, Vizcaino C, Patarroyo MA, Patarroyo ME (2010) Sequences of the Plasmodium falciparum cytoadherence-linked asexual protein 9 implicated in malaria parasite invasion to erythrocytes. Vaccine 28(14):2653–2663

    Article  PubMed  CAS  Google Scholar 

  • Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE (1995) Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. AmJTrop Med Hyg 52(6):565–568

    CAS  Google Scholar 

  • Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM (2007) Vivax malaria: neglected and not benign. AmJTrop Med Hyg 77(6 Suppl):79–87

    Google Scholar 

  • Rodriguez LE, Curtidor H, Urquiza M, Cifuentes G, Reyes C, Patarroyo ME (2008) Intimate molecular interactions of P. falciparum merozoite proteins involved in invasion of red blood cells and their implications for vaccine design. Chem Rev 108(9):3656–3705. doi:10.1021/cr068407v

    Article  PubMed  CAS  Google Scholar 

  • Sabbatani S, Fiorino S, Manfredi R (2010) The emerging of the fifth malaria parasite (Plasmodium knowlesi): a public health concern? Braz J Infect Dis 14(3):299–309

    PubMed  Google Scholar 

  • Sam-Yellowe TY (1993) Plasmodium falciparum: analysis of protein–protein interactions of the 140/130/110-kDa rhoptry protein complex using antibody and mouse erythrocyte binding assays. Exp Parasitol 77(2):179–194

    Article  PubMed  CAS  Google Scholar 

  • Sam-Yellowe TY, Perkins ME (1991) Interaction of the 140/130/110 kDa rhoptry protein complex of Plasmodium falciparum with the erythrocyte membrane and liposomes. Exp Parasitol 73(2):161–171

    Article  PubMed  CAS  Google Scholar 

  • Sam-Yellowe TY, Shio H, Perkins ME (1988) Secretion of Plasmodium falciparum rhoptry protein into the plasma membrane of host erythrocytes. J Cell Biol 106(5):1507–1513

    Article  PubMed  CAS  Google Scholar 

  • Shirano M, Tsuboi T, Kaneko O, Tachibana M, Adams JH, Torii M (2001) Conserved regions of the Plasmodium yoelii rhoptry protein RhopH3 revealed by comparison with the P. falciparum homologue. Mol Biochem Parasitol 112(2):297–299

    Article  PubMed  CAS  Google Scholar 

  • Topolska AE, Lidgett A, Truman D, Fujioka H, Coppel RL (2004) Characterization of a membrane-associated rhoptry protein of Plasmodium falciparum. J Biol Chem 279(6):4648–4656. doi:10.1074/jbc.M307859200M307859200

    Article  PubMed  CAS  Google Scholar 

  • Trenholme KR, Gardiner DL, Holt DC, Thomas EA, Cowman AF, Kemp DJ (2000) clag9: A cytoadherence gene in Plasmodium falciparum essential for binding of parasitized erythrocytes to CD36. Proc Natl Acad Sci U S A 97(8):4029–4033. doi:10.1073/pnas.040561197040561197

    Article  PubMed  CAS  Google Scholar 

  • Tsuboi T, Takeo S, Iriko H, Jin L, Tsuchimochi M, Matsuda S, Han ET, Otsuki H, Kaneko O, Sattabongkot J, Udomsangpetch R, Sawasaki T, Torii M, Endo Y (2008) Wheat germ cell-free system-based production of malaria proteins for discovery of novel vaccine candidates. Infect Immun 76(4):1702–1708

    Article  PubMed  CAS  Google Scholar 

  • Tsuboi T, Takeo S, Sawasaki T, Torii M, Endo Y (2010) An efficient approach to the production of vaccines against the malaria parasite. Methods Mol Biol 607:73–83. doi:10.1007/978-1-60327-331-2_8

    Article  PubMed  CAS  Google Scholar 

  • Vincensini L, Richert S, Blisnick T, Van Dorsselaer A, Leize-Wagner E, Rabilloud T, Braun Breton C (2005) Proteomic analysis identifies novel proteins of the Maurer’s clefts, a secretory compartment delivering Plasmodium falciparum proteins to the surface of its host cell. Mol Cell Proteomics 4(4):582–593

    Article  PubMed  CAS  Google Scholar 

  • Vincensini L, Fall G, Berry L, Blisnick T, Braun Breton C (2008) The RhopH complex is transferred to the host cell cytoplasm following red blood cell invasion by Plasmodium falciparum. Mol Biochem Parasitol 160(2):81–89

    Article  PubMed  CAS  Google Scholar 

  • Wang T, Fujioka H, Drazba JA, Sam-Yellowe TY (2006) Rhop-3 protein conservation among Plasmodium species and induced protection against lethal P. yoelii and P. berghei challenge. Parasitol Res 99(3):238–252. doi:10.1007/s00436-006-0136-9

    Article  PubMed  Google Scholar 

  • Yang JC, Blanton RE, King CL, Fujioka H, Aikawa M, Sam-Yellowe TY (1996) Seroprevalence and specificity of human responses to the Plasmodium falciparum rhoptry protein Rhop-3 determined by using a C-terminal recombinant protein. Infect Immun 64(9):3584–3591

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Hyoja2-dong, Chuncheon, Gangwon-do, 200-701, Republic of Korea

    Bo Wang, Feng Lu, Yang Cheng, Jian Li & Eun-Taek Han

  2. Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, 214064, People’s Republic of China

    Feng Lu & Jian Li

  3. Cell-free Science and Technology Research Center and Venture Business Laboratory, Ehime University, Matsuyama, Ehime, 790-8577, Japan

    Daisuke Ito & Takafumi Tsuboi

  4. Mahidol Vivax Research Center, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

    Jetsumon Sattabongkot

Authors
  1. Bo Wang
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  2. Feng Lu
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  3. Yang Cheng
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  6. Jetsumon Sattabongkot
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  7. Takafumi Tsuboi
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  8. Eun-Taek Han
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Correspondence to Eun-Taek Han.

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Wang, B., Lu, F., Cheng, Y. et al. Identification and characterization of the Plasmodium falciparum RhopH2 ortholog in Plasmodium vivax . Parasitol Res 112, 585–593 (2013). https://doi.org/10.1007/s00436-012-3170-9

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  • DOI: https://doi.org/10.1007/s00436-012-3170-9

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