title: The erythrocyte binding motif of plasmodium vivax duffy binding protein is highly polymorphic and functionally conserved in isolates from Papua New Guinea.
abstract: The Duffy binding protein (DBP) of Plasmodium vivax is a critical adhesion ligand that participates in merozoite invasion of human Duffy positive reticulocytes. Binding domains have been shown to lie within a conserved N-terminal cyteine-rich region, region II, that contains 330-aa and the critical binding residues have been recently mapped to 170-aa stretch within this region. Previous studies on few isolates indicated a significant degree of polymorphism in region II (DBPII). To examine further the degree of variability of DBPII, and whether these variants produce functional changes, DBPII was amplified by nested PCR from 24 isolates from Papua New Guinea, and the amplicons were cloned and sequenced. One synonymous and 18 non-synonymous mutations were identified. Altogether, 93% of the cumulative polymorphisms lie within the 170-aa region. Targeted surface expression of region II of two different alleles on the surface of Cos7 cells did not affect their binding to Duffy positive erythrocytes. These results indicate that polymorphisms in the critical binding motifs do not alter its function. If DBPII variation arose to avert mechanisms of protective immunity targeting the DBP, vaccine development employing the parasite binding ligand may require strategies to minimize the effect of this polymorphism.
authors.affiliation: Division of Geographic Medicine, Case Western Reserve University, Cleveland, OH 44106-4983, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xainli
authors.forename: J H
authors.initials: JH
authors.lastname: Adams
authors.forename: C L
authors.initials: CL
authors.lastname: King
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D000818:Animals; D000953:Antigens, Protozoan; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002675:Child, Preschool; D004375:Duffy Blood-Group System / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D017125:Genes, Protozoan; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000469:parasitology; D008969:Molecular Sequence Data; D010219:Papua New Guinea; D010966:Plasmodium vivax / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface