Whole Genome Sequencing of Field Isolates Reveals a Common Duplication of the Duffy Binding Protein Gene in Malagasy Plasmodium vivax Strains

Ménard, Didier; Chan, E. Ricky; Benedet, Christophe; Ratsimbasoa, Arsène; Kim, Saorin; Chim, Pheaktra; Do, Catherine; Witkowski, Benoît; Durand, Rémy; Thellier, Marc; Severini, Carlo; Legrand, Eric; Musset, Lise; Nour, Bakri Y. M.; Mercereau‐Puijalon, Odile; Serre, David; Zimmerman, Peter A.

doi:10.1371/journal.pntd.0002489

Cited by 111 publications

(144 citation statements)

References 29 publications

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…Recently, the whole-genome sequencing of P. vivax from a Duffy-positive patient in Madagascar has revealed copy number expansion of Duffy-binding protein 1, and the existence of these two DBP1 copies next to each other was confirmed by PCR (22). A recent publication describes the gene copy number variation of DBP1 in P. vivax from Western Thailand (2 and 3 copies), Western Cambodia (2 copies), Papua Indonesia (2 and 3 copies) (24).…”

Section: Resultsmentioning

confidence: 98%

“…Is it possible that mutations in the cysteine-rich region 2 of the P. vivax DBP1 allows binding to another protein on the surface of Duffy-null erythrocytes, unrelated to the Duffy? Alternatively, the widespread duplication of the gene encoding DBP1 observed in Madagascar (14,22) and the three and eight copies of DBP1 in the two Duffy-null P. vivax-infected patients in Ethiopia (present paper) may allow for low-affinity binding of DBP1 to a new receptor on Duffy-null erythrocytes.…”

Section: Dna Expansionmentioning

confidence: 84%

“…2A) (22). The DBP1 from Madagascar was duplicated, and both sequences were identical in the DBP1 domain except for a single amino acid difference in the signal sequence.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Gunalan

Hostetler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

View full text Add to dashboard Cite

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.Plasmodium vivax | Duffy blood group antigen | Duffy-binding protein | DNA expansionI n 1975 we identified the failure of Plasmodium knowlesi to invade Duffy-null erythrocytes (1). We assumed that the Duffy blood group null phenotype, a common African phenotype, conferred resistance in Africans to P. vivax, a Plasmodium closely related to P. knowlesi. Subsequent studies demonstrated that African American volunteers who were Duffy-null were resistant to mosquito-transmitted P. vivax (2). In addition, African American soldiers in Vietnam who were infected with P. vivax were all Duffypositive (3). Furthermore, African Americans in a village in Honduras who were infected with P. vivax were all Duffy-positive whereas those infected with P. falciparum were both Duffy-null and -positive (4). We concluded that Duffy null was the basis of resistance to P. vivax by Africans.The molecular basis of Duffy null was a single point mutation in the GATA1-binding sequence in the promotor region 5′ to the Duffy blood group ORF (Fig. 1B) that led to Duffy-blood-groupnull erythrocytes (5). In vitro studies with P. knowlesi demonstrated that the invasive merozoites were able to bind and reorient apically with Duffy-null erythrocytes but could not form a junction as occurred in Duffy-positive erythrocytes, indicating that the Duffy blood group was required for P. vivax invasion (6). Later, in P. knowlesi parasite culture supernatants, the parasite ligand binding to Duffy blood group antigen was identi...

show abstract

Section: Resultsmentioning

confidence: 98%

Section: Dna Expansionmentioning

confidence: 84%

See 1 more Smart Citation

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Gunalan

Hostetler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

View full text Add to dashboard Cite

show abstract

“…39 More recently, a small number of whole genome sequences have been analysed and confirm the high diversity of this species. 10,40,41 Presently, approximately 10 high quality full genome P. vivax sequences are publically available, yet this number is expected to increase in the near future thus allowing population genomic studies to be conducted on whole genomes. In comparison to P. falciparum, P. vivax has approximately two-fold more SNPs and significantly higher microsatellite diversity.…”

Section: Genomicsmentioning

confidence: 99%

Uncovering the transmission dynamics ofPlasmodium vivaxusing population genetics

Barry

Waltmann

Koepfli

et al. 2015

Pathogens and Global Health

View full text Add to dashboard Cite

Population genetic analysis of malaria parasites has the power to reveal key insights into malaria epidemiology and transmission dynamics with the potential to deliver tools to support control and elimination efforts. Analyses of parasite genetic diversity have suggested that Plasmodium vivax populations are more genetically diverse and less structured than those of Plasmodium falciparum indicating that P. vivax may be a more ancient parasite of humans and/or less susceptible to population bottlenecks, as well as more efficient at disseminating its genes. These population genetic insights into P. vivax transmission dynamics provide an explanation for its relative resilience to control efforts. Here, we describe current knowledge on P. vivax population genetic structure, its relevance to understanding transmission patterns and relapse and how this information can inform malaria control and elimination programmes.

show abstract

“…DBP-II is a three-subdomain (SD) protein, with SD2 contributing key residues for dimerization and receptor binding (19). Duffy-independent invasion has been reported for certain isolates of P. vivax (29); however, these isolates contain a gene duplication of DBP, suggesting that increased expression of DBP may facilitate Duffy-negative invasion (30).…”

mentioning

confidence: 99%

Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein

Chen

Salinas

Huang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

129

View full text Add to dashboard Cite

Plasmodium vivax Duffy Binding Protein (PvDBP) is the most promising vaccine candidate for P. vivax malaria. The polymorphic nature of PvDBP induces strain-specific immune responses, however, and the epitopes of broadly neutralizing antibodies are unknown. These features hamper the rational design of potent DBP-based vaccines and necessitate the identification of globally conserved epitopes. Using X-ray crystallography, small-angle X-ray scattering, hydrogen-deuterium exchange mass spectrometry, and mutational mapping, we have defined epitopes for three inhibitory mAbs (mAbs 2D10, 2H2, and 2C6) and one noninhibitory mAb (3D10) that engage DBP. These studies expand the currently known inhibitory epitope repertoire by establishing protective motifs in subdomain three outside the receptor-binding and dimerization residues of DBP, and introduce globally conserved protective targets. All of the epitopes are highly conserved among DBP alleles. The identification of broadly conserved epitopes of inhibitory antibodies provides critical motifs that should be retained in the next generation of potent vaccines for P. vivax malaria.

show abstract

Whole Genome Sequencing of Field Isolates Reveals a Common Duplication of the Duffy Binding Protein Gene in Malagasy Plasmodium vivax Strains

Cited by 111 publications

References 29 publications

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Uncovering the transmission dynamics ofPlasmodium vivaxusing population genetics

Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein

Contact Info

Product

Resources

About