Red cell antigen, serum protein, and red cell enzyme polymorphisms in inhabitants of the Jimi Valley, Western Highlands, New Guinea

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

doi:10.1007/bf00278860

Cited by 5 publications

(1 citation statement)

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“…Why has P. falciparum evolved so many pathways for invasion? The erythrocyte surface molecules are highly polymorphic within the human population (34)(35)(36)(37)(38). It has been reported that the fastest evolving genes in the human lineage are the glycophorins A and B (39).…”

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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