Role ofPlasmodium vivaxDuffy-binding protein 1 in invasion of Duffy-null Africans

Abstract

The ability of the malaria parasitePlasmodium vivaxto invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible toP. vivaxinfections. Recently,P. vivaxinfections in Duffy-null Africans have been documented, raising the possibility thatP. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa.P. vivaxbinds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability ofP. vivaxto bind Duffy-null erythrocytes, we analyzedP. vivaxparasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side-by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability ofP. vivaxto infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-nullP. vivaxinfections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy-null erythrocytes. Indeed, we show that Salvador (Sal) IP. vivaxinfects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude thatP. vivaxSal I and perhapsP. vivaxin Duffy-null patients may have adapted to use new ligand–receptor pairs for invasion.