title: Baculovirus-expressed Plasmodium reichenowi EBA-140 merozoite ligand is host specific.
abstract: Plasmodium reichenowi, an ape malaria parasite is morphologically identical and genetically similar to Plasmodium falciparum, infects chimpanzees but not humans. Genomic studies revealed that all primate malaria parasites belong to Laverania subgenus. Laverania parasites exhibit strict host specificity, but the molecular mechanisms underlying these host restrictions remain unexplained. Plasmodium merozoites express multiple binding ligands that recognize specific receptors on erythrocytes, including micronemal proteins belonging to P. falciparum EBL family. It was shown that erythrocyte binding antigen-175 (EBA-175), erythrocyte binding ligand-1 (EBL-1), erythrocyte binding antigen-140 (EBA-140) recognize erythrocyte surface sialoglycoproteins - glycophorins A, B, C, respectively. EBA-140 merozoite ligand hijacks glycophorin C (GPC), a minor erythrocyte sialoglycoprotein, to invade the erythrocyte through an alternative invasion pathway. A homolog of P. falciparum EBA-140 protein was identified in P. reichenowi. The amino acid sequences of both EBA-140 ligands are very similar, especially in the conservative erythrocyte binding region (Region II). It has been suggested that evolutionary changes in the sequence of EBL proteins may be associated with Plasmodium host restriction. In this study we obtained, for the first time, the recombinant P. reichenowi EBA-140 ligand Region II using baculovirus expression vector system. We show that the ape EBA-140 Region II is host specific and binds to chimpanzee erythrocytes in the dose and sialic acid dependent manner. Further identification of the erythrocyte receptor for this ape ligand is of great interests, since it may reveal the molecular basis of host restriction of both P. reichenowi and its deadliest human counterpart, P. falciparum.
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Zerka
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Olechwier
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rydzak
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Kaczmarek
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; Department of Molecular Biology, University of Zielona Góra, Zielona Góra, Poland. Electronic address: ewa.jaskiewicz@iitd.pan.wroc.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jaskiewicz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002942:Circular Dichroism; D004912:Erythrocytes / Q000378:metabolism*; D006021:Glycophorins / Q000378:metabolism*; D058507:Host Specificity / Q000235:genetics*; D008565:Membrane Proteins; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D002679:Pan troglodytes; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D061987:Sf9 Cells; D020349:Surface Plasmon Resonance
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; C066001:Duffy antigen binding protein, Plasmodium; C438380:EBA140 protein, Plasmodium falciparum; D006021:Glycophorins; D008565:Membrane Proteins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C065668:erythrocyte-binding antigen 175, Plasmodium; D019158:N-Acetylneuraminic Acid
keywords: Baculovirus expression vector system; Chimpanzee EBA-140 merozoite ligand; Host specificity; Plasmodium evolution; Plasmodium reichenowi