The erythrocyte binding motif of Plasmodium vivax Duffy binding protein ishighly polymorphic and functionally conserved in isolates from Papua New Guinea

The Duffy binding protein (DBP) of Plasmodium vivax is a critical adhesion ligand that participates in merozoite invasion of human Duffy positive reti culocytes. Binding domains have been shown to lie within a conserved N-term inal cyteine-rich region, region II, that contains 330-aa and the critical binding residues have been recently mapped to 170-aa stretch within this re gion. Previous studies on few isolates indicated a significant degree of po lymorphism in region II (DBPII). To examine further the degree of variabili ty of DBPII, and whether these variants produce functional changes, DBPII w as amplified by nested PCR from 24 isolates from Papua New Guinea, and the amplicons were cloned and sequenced. One synonymous and 18 non-synonymous m utations were identified. Altogether, 93% of the cumulative polymorphisms l ie within the 170-aa region. Targeted surface expression of region II of tw o different alleles on the surface of Cos7 cells did not affect their bindi ng to Duffy positive erythrocytes. These results indicate that polymorphism s in the critical binding motifs do not alter its function. If DBPII variat ion arose to avert mechanisms of protective immunity targeting the DBP, vac cine development employing the parasite binding ligand may require strategi es to minimize the effect of this polymorphism. (C) 2000 Elsevier Science B .V. All rights reserved.