Duffy-null promoter heterozygosity reduces DARC expression and abrogates adhesion of the P. vivax ligand required for blood-stage infection.
The Duffy blood group antigen is an essential receptor for Plasmodium vivax entry into erythrocytes in a process mediated by the parasite ligand, the Duffy binding protein (DBP). Recently, individuals living in a malaria endemic region of Papua New Guinea were identified as heterozygous for a new allele conferring Duffy negativity, which results in 50% less Duffy antigen on their erythrocytes. We demonstrate that DBP adherence to erythrocytes is significantly reduced for erythrocytes from heterozygous individuals who carry one Duffy antigen negativity allele. These data provide evidence that emergence of this new allelic form of Duffy negativity is correlated with resistance against vivax malaria.
Michon
P
P
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556-0369, USA.
Woolley
I
I
Wood
E M
EM
Kastens
W
W
Zimmerman
P A
PA
Adams
J H
JH
D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan; D002352:Carrier Proteins / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D004375:Duffy Blood-Group System; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D008024:Ligands; D016780:Malaria, Vivax / Q000235:genetics*; D010219:Papua New Guinea; D010966:Plasmodium vivax / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000235:genetics*
C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D008024:Ligands; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface