Red Cell Antigen, Serum Protein and Red Cell Enzyme Polymorphisms in Karkar Islanders and Inhabitants of the Adjacent North Coast of New Guinea

Booth, P. B.; Tills, D.; Warlow, A.; Kopeć, Ada C.; Mourant, A. E.; Teesdale, Phyllis; Hornabrook, R. W.

doi:10.1159/000153328

Cited by 15 publications

(9 citation statements)

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“…There are at least 40 blood types that are caused by variations in glycophorin A and B (40), many of which occur in Africa. Gerbich-negative polymorphism of glycophorin C occurs in 50% of the population of a malaria endemic region of Papua, New Guinea (41,42) and is the erythrocyte receptor for one variant of BAEBL (15,20). The erythrocyte receptors for JESEBL͞EBA-181 have not been identified.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism in the Plasmodium falciparum erythrocyte-binding ligand JESEBL/EBA-181 alters its receptor specificity

Mayer

Kaneko

et al. 2004

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

107

138

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The malaria parasite lives within erythrocytes and depends on the binding of parasite ligands to host cell surface receptors for invasion. The most virulent human malaria parasite, Plasmodium falciparum, uses multiple ligands, including EBA-175, BAEBL, and JESEBL of the Duffy-binding-like (DBL) family of erythrocytebinding proteins, for invasion of human erythrocytes. Region II of these parasite ligands is the erythrocyte-binding domain. Previously, we had shown that polymorphism in region II of BAEBL leads to different erythrocyte-binding specificities. We have now identified and characterized the binding specificity of six JESEBL variants. We sequenced region II of JESEBL from 20 P. falciparum clones collected from various parts of the world where malaria is endemic. We observed eight JESEBL variants that contained amino acid polymorphisms at five positions among all clones. Seven of the eight variants could be connected by a single base change that led to an amino acid change. We investigated the functional significance of these polymorphisms by transiently expressing region II from six of JESEBL variants on the surface of Chinese hamster ovary cells. We observed four erythrocyte-binding patterns to enzymetreated erythrocytes. Thus, P. falciparum DBL ligands JESEBL and BAEBL can recognize multiple receptors on the erythrocyte surface. In contrast to Plasmodium vivax, which has disappeared from West Africa because of the Duffy-negative blood group, P. falciparum may have been successful in endemic areas because it has mutated the ligands of the DBL family to create multiple pathways of invasion, thus making selection of refractory erythrocytes unlikely.parasite polymorphism A ll of the clinical manifestations associated with human malaria infection are due to the asexual erythrocytic phase of the Plasmodium life cycle. Although the process by which the parasite enters erythrocytes is complex and not well understood, invasion of erythrocytes by Plasmodium can be divided into multiple steps. Initial attachment of the parasite to the erythrocyte is followed by reorientation to bring the apical end of the parasite into close contact with the surface of the erythrocyte (1). The parasite forms a junction between its apical end and the erythrocyte surface. Junction formation is irreversible and is followed by entry through invagination of the erythrocyte membrane (2). The process of junction formation is mediated by interaction between specific erythrocyte receptors and specific parasite ligands, as indicated by the inability of Plasmodium knowlesi, a simian malaria parasite that can infect humans, to form a junction with human erythrocytes lacking the Duffy blood group antigen and Plasmodium vivax to invade erythrocytes and infect Duffy-negative individuals (3-5).Unlike P. vivax, which is restricted to the erythrocytes expressing the Duffy blood group antigen and to reticulocytes, invasion of human erythrocytes by Plasmodium falciparum involves a number of apparently redundant receptor-ligand interactions between th...

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Section: Discussionmentioning

confidence: 99%

Polymorphism in the Plasmodium falciparum erythrocyte-binding ligand JESEBL/EBA-181 alters its receptor specificity

Mayer

Kaneko

et al. 2004

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

107

138

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“…The Gerbich phenotype is found at high allele frequencies (50%) in some regions of Papua New Guinea (26). The mutation consists of a deletion of exon 3 in glycophorin C that leads to truncated glycophorin C and missing glycophorin D (27).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Plasmodium falciparum erythrocyte-binding protein paralogous to EBA-175

Mayer

Kaneko

Hudson-Taylor

et al. 2001

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

163

132

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A member of a Plasmodium receptor family for erythrocyte invasion was identified on chromosome 13 from the Plasmodium falciparum genome sequence of the Sanger Centre (Cambridge, U.K.). The protein (named BAEBL) has homology to EBA-175, a P. falciparum receptor that binds specifically to sialic acid and the peptide backbone of glycophorin A on erythrocytes. Both EBA-175 and BAEBL localize to the micronemes, organelles at the invasive ends of the parasites that contain other members of the family. Like EBA-175, the erythrocyte receptor for BAEBL is destroyed by neuraminidase and trypsin, indicating that the erythrocyte receptor is a sialoglycoprotein. Its specificity, however, differs from that of EBA-175 in that BAEBL can bind to erythrocytes that lack glycophorin A, the receptor for EBA-175. It has reduced binding to erythrocytes with the Gerbich mutation found in another erythrocyte, sialoglycoprotein (glycophorin C͞D). The interest in BAEBL's reduced binding to Gerbich erythrocytes derives from the high frequency of the Gerbich phenotype in some regions of Papua New Guinea where P. falciparum is hyperendemic.

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“…The Ge − phenotype is caused by the deletion of exon 3 in the glycophorin C gene (GYPCΔex3; human chromosome 2q14-q21) and is found in Hardy-Weinberg equilibrium in malaria holoendemic regions of PNG [7][8][9][10][11][12][13]. Glycophorin C (128 amino acid residues, apparent 35 kDa, integral membrane sialoglycoprotein) [10] is a physiologically important monomer that interacts with the peripheral membrane protein 4.1 to mediate attachment of the sub-membranous cytoskeleton to the erythrocyte membrane.…”

Section: Gerbich-negativity and Field Studies In Pngmentioning

confidence: 99%

Erythrocyte polymorphisms and malaria parasite invasion in Papua New Guinea

Zimmerman

Patel

Maier

et al. 2003

Trends in Parasitology

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Plasmodium falciparum merozoites engage the erythrocyte surface through several receptor (host)-ligand (parasite) interactions during a brief exchange that results in parasite invasion of the red blood cell. Tens of thousands of these events occur during the initial cycle of blood-stage infections but advance towards billions as the parasite becomes visible to microscopists attempting to diagnose the underlying cause of illness in febrile patients. Advancing blood-stage infection leads to massive proportions of erythrocytes that rupture during repetitive cycles of asexual reproduction. As the infection leads to illness, non-immune or semi-immune individuals can suffer from life-threatening consequences of severe malarial anemia that play a leading role in pathogenesis. Through natural selection, some erythrocyte membrane polymorphisms are likely to have reduced the invasion success of the P. falciparum merozoite and increased the fitness of the human host population.In the mid-1970s, initial insights into the molecular nature of the interactions between erythrocyte surface proteins and malaria parasites were gained using Plasmodium knowlesi, a simian parasite amenable to in vitro culture [1]. These studies ultimately led to the discovery that the erythrocyte membrane protein carrying the Duffy blood group was a crucial invasion receptor for Plasmodium knowlesi and the related human parasite Plasmodium vivax [2,3]. These seminal experiments performed by Louis Miller and his colleagues paved the way to the exploration of two key concepts that underlie susceptibility of the red blood cell to malaria infection [4]. First, specific proteins on the erythrocyte surface are co-opted by the merozoite to activate and promote parasite invasion [5,6]. This hypothesis implies that parasite proteins somehow bind erythrocyte receptors and work in partnership as the merozoite pulls itself into the cell and forms the parasitophorous vacuole. Second, polymorphisms that modify the structure or level of expression of erythrocyte membrane proteins alter the efficiency of invasion and, ultimately, susceptibility to malaria. As malaria kills millions of children each year in endemic areas, mutations that diminish the efficiency of the invasion process would confer a selective advantage to the host and might be expected to increase in frequency over time through natural selection. Given the relatively short generation time of malaria compared with humans (asexual stages of 2-4

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Red Cell Antigen, Serum Protein and Red Cell Enzyme Polymorphisms in Karkar Islanders and Inhabitants of the Adjacent North Coast of New Guinea

Cited by 15 publications

References 1 publication

Polymorphism in the Plasmodium falciparum erythrocyte-binding ligand JESEBL/EBA-181 alters its receptor specificity

Polymorphism in the Plasmodium falciparum erythrocyte-binding ligand JESEBL/EBA-181 alters its receptor specificity

Characterization of a Plasmodium falciparum erythrocyte-binding protein paralogous to EBA-175

Erythrocyte polymorphisms and malaria parasite invasion in Papua New Guinea

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