title: Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans.
abstract: The ability of the malaria parasite Plasmodium vivax to 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 to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy-null erythrocytes, we analyzed P. vivax parasites 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 of P. vivax to infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections 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) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand-receptor pairs for invasion.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
authors.forename: Karthigayan
authors.initials: K
authors.lastname: Gunalan
authors.affiliation: Program in Public Health, College of Health Sciences, University of California, Irvine, CA 92697;
authors.forename: Eugenia
authors.initials: E
authors.lastname: Lo
authors.affiliation: Laboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; Malaria Programme, Wellcome Trust, Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1RQ, United Kingdom;
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Hostetler
authors.affiliation: Department of Medical Laboratory Sciences and Pathology, College of Health Sciences, Jimma University, Jimma 5195, Ethiopia; Tropical and Infectious Diseases Research Center, Jimma University, Jimma 5195, Ethiopia;
authors.forename: Delenasaw
authors.initials: D
authors.lastname: Yewhalaw
authors.affiliation: Laboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mu
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Neafsey
authors.affiliation: Program in Public Health, College of Health Sciences, University of California, Irvine, CA 92697;
authors.forename: Guiyun
authors.initials: G
authors.lastname: Yan
authors.affiliation: Laboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; lmiller@niaid.nih.gov.
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
mesh_terms: D000349:Africa / Q000453:epidemiology; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics*; D056915:DNA Copy Number Variations; D004375:Duffy Blood-Group System / Q000235:genetics; D004912:Erythrocytes / Q000469:parasitology* / Q000473:pathology; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology / Q000235:genetics / Q000469:parasitology* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010966:Plasmodium vivax / Q000235:genetics*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics*; D012453:Saimiri
chemical_list: D000953:Antigens, Protozoan; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface
keywords: DNA expansion; Duffy blood group antigen; Duffy-binding protein; Plasmodium vivax