A Plasmodium falciparum homologue of Plasmodium vivax reticulocyte binding protein (PvRBP1) defines a trypsin-resistant erythrocyte invasion pathway.
Invasion of erythrocytes by Plasmodium merozoites is an intricate process involving multiple receptor-ligand interactions. The glycophorins and an unknown trypsin sensitive factor are all erythrocyte receptors used during invasion by the major human pathogen Plasmodium falciparum. However, only one erythrocyte receptor, Glycophorin A, has a well-established cognate parasite ligand, the merozoite protein erythrocyte binding antigen-175 (EBA-175). The involvement of several other parasite proteins during invasion have been proposed, but no direct evidence links them with a specific invasion pathway. Here we report the identification and characterization of P. falciparum normocyte binding protein 1 (PfNBP1), an ortholog of Plasmodium vivax reticulocyte binding protein-1. PfNBP1 binds to a sialic acid dependent trypsin-resistant receptor on the erythrocyte surface that appears to be distinct from known invasion receptors. Antibodies against PfNBP1 can inhibit invasion of trypsinized erythrocytes and two P. falciparum strains that express truncated PfNBP1 are unable to invade trypsinized erythrocytes. One of these strain, 7G8, also does not invade Glycophorin B-negative erythrocytes. PfNBP1 therefore defines a novel trypsin-resistant invasion pathway and adds a level of complexity to current models for P. falciparum erythrocyte invasion.
Rayner
J C
JC
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Chamblee, GA 30341, USA.
Vargas-Serrato
E
E
Huber
C S
CS
Galinski
M R
MR
Barnwell
J W
JW
D000818:Animals; D000913:Antibodies, Protozoan / Q000378:metabolism; D001483:Base Sequence; D018076:DNA, Complementary; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D010966:Plasmodium vivax / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism*
D000913:Antibodies, Protozoan; D018076:DNA, Complementary; D008565:Membrane Proteins; D015800:Protozoan Proteins; C443160:normocyte binding protein 1, plasmodium falciparum; C075483:reticulocyte-binding protein, Plasmodium vivax; D014357:Trypsin