The domain on the Duffy blood group antigen for binding Plasmodium vivax and P. knowlesi malarial parasites to erythrocytes.

Chitnis, Chetan E.; Chaudhuri, Asok; Horuk, Richard; Pogo, A.O.; Miller, Louis H.

doi:10.1084/jem.184.4.1531

Cited by 169 publications

(142 citation statements)

References 19 publications

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“…Critical binding motifs in PvDBPII have been mapped to a 170 amino acid stretch (amino acids 291-460), which includes cysteines 5-8 [11,12]. PvDBPII shows the highest genetic diversity compared to the remaining PvDBP regions and appears to be under strong selective pressure [13,14].…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Kang

Moon

Kim

et al. 2012

Malar J

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BackgroundPlasmodium vivax Duffy binding protein (PvDBP) plays an essential role in erythrocyte invasion and a potential asexual blood stage vaccine candidate antigen against P. vivax. The polymorphic nature of PvDBP, particularly amino terminal cysteine-rich region (PvDBPII), represents a major impediment to the successful design of a protective vaccine against vivax malaria. In this study, the genetic polymorphism and natural selection at PvDBPII among Myanmar P. vivax isolates were analysed.MethodsFifty-four P. vivax infected blood samples collected from patients in Myanmar were used. The region flanking PvDBPII was amplified by PCR, cloned into Escherichia coli, and sequenced. The polymorphic characters and natural selection of the region were analysed using the DnaSP and MEGA4 programs.ResultsThirty-two point mutations (28 non-synonymous and four synonymous mutations) were identified in PvDBPII among the Myanmar P. vivax isolates. Sequence analyses revealed that 12 different PvDBPII haplotypes were identified in Myanmar P. vivax isolates and that the region has evolved under positive natural selection. High selective pressure preferentially acted on regions identified as B- and T-cell epitopes of PvDBPII. Recombination may also be played a role in the resulting genetic diversity of PvDBPII.ConclusionsPvDBPII of Myanmar P. vivax isolates displays a high level of genetic polymorphism and is under selective pressure. Myanmar P. vivax isolates share distinct types of PvDBPII alleles that are different from those of other geographical areas. These results will be useful for understanding the nature of the P. vivax population in Myanmar and for development of PvDBPII-based vaccine.

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Section: Introductionmentioning

confidence: 99%

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Kang

Moon

Kim

et al. 2012

Malar J

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“…Plasmodium vivax uses the Duffy antigen receptor (DARC) for entry into erythroid cells [3]. Human immunodeficiency virus-1 (HIV-1) and HIV-2 utilize specific chemokine receptors as co-receptors with CD4 to invade immune cells [4].…”

Section: Introductionmentioning

confidence: 99%

Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function

Howard

Korte

Tarasova

et al. 1998

Journal of Leukocyte Biology

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“…Adhesion to DA is mediated by the 140-kDa PvDBP (6)(7)(8). The receptor-binding domain of PvDBP maps to the conserved, N-terminal cysteine-rich region II (PvDBPII) (9,10). Given the complete dependence of P. vivax on the PvDBPII-Duffy interaction for blood-stage infection and recent observations that PvDBPII-specific antibodies inhibit P. vivax invasion of human erythrocytes in vitro (11), we examined the hypothesis that naturally acquired PvDBPII-specific binding inhibitory antibodies (BIAbs) are associated with protection against P. vivax infection in vivo.…”

mentioning

confidence: 99%

Naturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infection

King

Michon

Shakri

et al. 2008

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

158

209

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Individuals residing in malaria-endemic regions acquire protective immunity after repeated infection with malaria parasites; however, mechanisms of protective immunity and their immune correlates are poorly understood. Blood-stage infection with Plasmodium vivax depends completely on interaction of P. vivax Duffy-binding protein (PvDBP) with the Duffy antigen on host erythrocytes. Here, we performed a prospective cohort treatment/reinfection study of children (5-14 years) residing in a P. vivax-endemic region of Papua New Guinea (PNG) in which children were cleared of blood-stage infection and then examined biweekly for reinfection for 25 weeks. To test the hypothesis that naturally acquired binding inhibitory antibodies (BIAbs) targeting PvDBP region II (PvDBPII) provide protection against P. vivax infection, we used a quantitative receptor-binding assay to distinguish between antibodies that merely recognize PvDBP and those that inhibit binding to Duffy. The presence of high-level BIAbs (>90% inhibition of PvDBPII-Duffy binding, n ‫؍‬ 18) before treatment was associated with delayed time to P. vivax reinfection diagnosed by light microscopy (P ‫؍‬ 0.02), 55% reduced risk of P. vivax reinfection (Hazard's ratio ‫؍‬ 0.45, P ‫؍‬ 0.04), and 48% reduction in geometric mean P. vivax parasitemia (P < 0.001) when compared with children with low-level BIAbs (n ‫؍‬ 148). Further, we found that stable, high-level BIAbs displayed strain-transcending inhibition by reducing reinfection with similar efficiency of PNG P. vivax strains characterized by six diverse PvDBPII haplotypes. These observations demonstrate a functional correlate of protective immunity in vivo and provide support for developing a vaccine against P. vivax malaria based on PvDBPII.Duffy antigen ͉ immunity ͉ protective antibodies P rotective immunity against malaria is acquired by residents of endemic regions over a period of years after repeated exposure to malaria parasites (1). Naturally acquired immunity to Plasmodium falciparum and Plasmodium vivax malaria does not prevent infection by these parasites completely, but limits parasite densities, reduces the frequency of clinical malaria episodes, and prevents severe disease (2). Humoral immune responses against blood-stage antigens are an important component of naturally acquired immunity to malaria (2, 3). Therefore, parasite proteins engaged in erythrocyte invasion are potential targets of protective antibody responses.Interaction between P. vivax Duffy-binding protein (PvDBP) and the Duffy antigen receptor (DA) on host erythrocytes is central to blood-stage infection by P. vivax (4, 5). Adhesion to DA is mediated by the 140-kDa PvDBP (6-8). The receptor-binding domain of PvDBP maps to the conserved, N-terminal cysteine-rich region II (PvDBPII) (9, 10). Given the complete dependence of P. vivax on the PvDBPII-Duffy interaction for blood-stage infection and recent observations that PvDBPII-specific antibodies inhibit P. vivax invasion of human erythrocytes in vitro (11), we examined the hypothesis that...

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The domain on the Duffy blood group antigen for binding Plasmodium vivax and P. knowlesi malarial parasites to erythrocytes.

Cited by 169 publications

References 19 publications

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function

Naturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infection

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