Volume 80, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The region II of Duffy binding protein (PvDBP–II) contains the critical binding residues, which is a major target for development of naturally acquired immunity. Several studies showed sequence polymorphisms in PvDBP–II, which may inhibit antibodies recognition. Therefore, in this study the level of PvDBP–II polymorphism within and among populations from re-emerged areas in north and endemic areas in south of Iran were evaluated by sequencing analysis in 75 isolates for the first time. Fourteen non-synonymous and one synonymous mutations were identified and none of the amino acid substitutions were directly involved in erythrocyte binding. Only 6 out of 14 detected mutations have been found among northern isolates, including D384G, R390H, N417K, L424I, W437R, and I503K. In total, two and nine different variants have been identified among northern and southern isolates, respectively. High association of the amino acid frequencies for codons 417, 437, and 503 were found among northern (85% for trio association and 100% for N417K with W437R), and southern (36% for trio association and 98% for N417K with W437R) samples. Polymorphisms at positions R308S, K371E, D384G, K386N, R390H, N417K, L424I, W437R, and I503K were identified from Iran and diverse geographic areas; however, mutation at position F306L was only reported from Asian malaria endemic areas. It is suggested that to develop polyvalent vaccine against infection, it is better to incorporate the common and high prevalent allelic variants of the antigen that were reported from different malaria endemic regions.


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  1. Mendis K, Sina BJ, Marchesini P, Carter R, 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64 : 97–106. [Google Scholar]
  2. Sharma VP, 1999. Current scenario of malaria in India. Parassitologia 41 : 349–353. [Google Scholar]
  3. San Sebastian M, Jativa R, Goicolea I, 2000. Epidemiology of malaria in the Amazon basin of Ecuador. Rev Panam Salud Publica 7 : 24–28. [Google Scholar]
  4. Palmer CJ, Makler M, Klaskala WI, Lindo JF, Baum MK, Ager AL, 1998. Increased prevalence of Plasmodium falciparum malaria in Honduras, Central America. Rev Panam Salud Publica 4 : 40–42. [Google Scholar]
  5. Collins WE, Jeffery GM, 1996. Primaquine resistance in Plasmodium vivax. Am J Trop Med Hyg 55 : 243–249. [Google Scholar]
  6. Miller LH, Mason SJ, Clyde DF, McGinniss MH, 1976. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N Engl J Med 295 : 302–304. [Google Scholar]
  7. Adams JH, Sim BK, Dolan SA, Fang X, Kaslow DC, Miller LH, 1992. A family of erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci USA 89 : 7085–7089. [Google Scholar]
  8. Chitnis CE, Miller LH, 1994. Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. J Exp Med 180 : 497–506. [Google Scholar]
  9. Sim BK, Orlandi PA, Haynes JD, Klotz FW, Carter JM, Camus D, Zegans ME, Chulay JD, 1990. Primary structure of the 175K Plasmodium falciparum erythrocyte binding antigen and identification of a peptide which elicits antibodies that inhibit malaria merozoite invasion. J Cell Biol 111 : 1877–1884. [Google Scholar]
  10. Sim BK, Chitnis CE, Wasniowska K, Hadley TJ, Miller LH, 1994. Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum. Science 264 : 1941–1944. [Google Scholar]
  11. Chitnis CE, Chaudhuri A, Horuk R, Pogo AO, Miller LH, 1996. The domain on the Duffy blood group antigen for binding Plasmodium vivax and P. knowlesi malarial parasites to erythrocytes. J Exp Med 184 : 1531–1536. [Google Scholar]
  12. Ranjan A, Chitnis CE, 1999. Mapping regions containing binding residues within functional domains of Plasmodium vivax and Plasmodium knowlesi erythrocyte–binding proteins. Proc Natl Acad Sci USA 96 : 14067–14072. [Google Scholar]
  13. Ampudia E, Patarroyo MA, Patarroyo ME, Murillo LA, 1996. Genetic polymorphism of the Duffy receptor binding domain of Plasmodium vivax in Colombian wild isolates. Mol Biochem Parasitol 78 : 269–272. [Google Scholar]
  14. Xainli J, Adams JH, King CL, 2000. The erythrocyte binding motif of Plasmodium vivax Duffy binding protein is highly polymorphic and functionally conserved in isolates from Papua New Guinea. Mol Biochem Parasitol 111 : 253–260. [Google Scholar]
  15. Cole–Tobian J, Cortes A, Baisor M, Kastens W, Xainli J, Bockarie M, Adams JH, King CHL, 2002. Age-acquired immunity to a Plasmodium vivax invasion ligand, the Duffy binding protein. J Infect Dis 186 : 531–539. [Google Scholar]
  16. Zimmerman PA, Woolley I, Masinde GL, Miller SM, McNamara DT, Hazlett F, Mgone CHS, Alpers MP, Genton B, Boatini BA, Kazura JW, 1999. Emergence of FY*A(null) in a Plasmodium vivax–endemic region of Papua New Guinea. Proc Natl Acad Sci USA 96 : 13973–13977. [Google Scholar]
  17. Grimberg BT, Udomsangpetch R, Xainli J, McHenry A, Panichakul T, Sattabongkot J, Cui L, Bockarie M, Chitnis CE, Adams J, Zimmerman PA, King CHL, 2007. Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Med 4 : 1940–1947. [Google Scholar]
  18. Ryan JR, Stoute JA, Amon J, Dunton RF, Mtalib R, Koros J, Owour B, Luckhart SH, Wirtz RA, Barnwell JW, Rosenberg R, 2006. Evidence for transmission of Plasmodium vivax among a Duffy antigen negative population in western Kenya. Am J Trop Med Hyg 75 : 575–581. [Google Scholar]
  19. Tsuboi T, Kappe SH, Al-Yaman F, Prickett MD, Alpers M, Adams JH, 1994. Natural variation within the principal adhesion domain of the Plasmodium vivax Duffy binding protein. Infect Immun 62 : 5581–5586. [Google Scholar]
  20. Hans D, Pattnaik P, Bhattacharyy A, Shakri AR, Yazdani SSH, Sharma M, Choe H, Farzan M, Chitnis CE, 2005. Mapping binding residues in the Plasmodium vivax domain that binds Duffy antigen during red cell invasion. Mol Microbiol 55 : 1423–1434. [Google Scholar]
  21. VanBuskirk KM, Sevova E, Adams JH, 2004. Conserved residues in the Plasmodium vivax Duffy-binding protein ligand domain are critical for erythrocyte receptor recognition. Proc Natl Acad Sci USA 101 : 15754–15759. [Google Scholar]
  22. Singh SK, Hora R, Belrhali H, Chitnis CE, Sharma A, 2006. Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain. Nature 439 : 741–744. [Google Scholar]
  23. Chitnis CE, Sharma A, 2008. Targeting the Plasmodium vivax Duffy-binding protein. Trends Parasitol 241 : 29–34. [Google Scholar]
  24. Baum J, Thomas AW, Conway DJ, 2003. Evidence for diversifying selection on erythrocyte-binding antigens of Plasmodium falciparum and P. vivax. Genetics 163 : 1327–1336. [Google Scholar]
  25. Kho WG, Chung JY, Sim EJ, Kim DW, Chung WCH, 2001. Analysis of polymorphic regions of Plasmodium vivax Duffy binding protein of Korean isolates. Korean J Parasitol 39 : 143–150. [Google Scholar]
  26. Sousa TN, Ceravolo IP, Frnandes Fontes CJ, Couto A, Carvalho LH, Brito CFA, 2006. The pattern of major polymorphisms in the Duffy binding protein ligand domain from the Brazilian Amazon area. Mol Biochem Parasitol 146 : 251–254. [Google Scholar]
  27. Zakeri S, Mehrizi AA, Mamaghani S, Noorizadeh S, Snounou G, Djadid ND, 2006. Population structure analysis of Plasmodium vivax in areas of Iran with different malaria endemicity. Am J Trop Med Hyg 74 : 394–400. [Google Scholar]
  28. Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN, 1993. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol 61 : 315–320. [Google Scholar]
  29. Van Buskirk KM, Jennifer L, Cole–Tobian JL, Baisor M, Sevova ES, Bockarie M, King CL, Adams JH, 2004. Antigenic drift in the ligand domain of Plasmodium vivax Duffy binding protein confers resistance to inhibitory antibodies. J Infect Dis 190 : 1556–1562. [Google Scholar]
  30. Gosi P, Khusmith S, Khalambaheti T, Lanar DE, Schaecher KE, Fukuda MM, Miller SR, 2008. Polymorphism patterns in Duffy-binding protein among Thai Plasmodium vivax isolates. Malar J 7 : 117. [Google Scholar]
  31. Tamura K, Dudley J, Nei M, Kumar S, 2007. MEGA 4.0: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24 : 1596–1599. [Google Scholar]
  32. Cole-Tobian J, King CHL, 2003. Diversity and natural selection in Plasmodium vivax Duffy binding protein gene. Mol Biochem Parasitol 127 : 121–132. [Google Scholar]
  33. Cole-Tobian JL, Michon P, Dabod E, Mueller L, King CL, 2007. Dynamics of asymptomatic Plasmodium vivax infections and Duffy binding protein polymorphisms in relation to parasitemia levels in Papua New Guinean children. Am J Trop Med Hyg 75 : 955–962. [Google Scholar]
  34. Clyde DF, 1975. Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites. Am J Trop Med Hyg 24 : 397–401. [Google Scholar]
  35. Zakeri S, Abouie A, Djadid ND, Snounou G, 2006. Circumsporozoite protein gene diversity among temperate and tropical Plasmodium vivax isolates from Iran. Trop Med Int Health 11 : 729–737. [Google Scholar]
  36. Fang XD, Kaslow DC, Adams JH, Miller LH, 1991. Cloning of the Plasmodium vivax Duffy receptor. Mol Biochem Parasitol 295 : 302–304. [Google Scholar]

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  • Received : 12 May 2008
  • Accepted : 19 Sep 2008

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