title: Reticulocyte-binding protein homologue 1 is required for sialic acid-dependent invasion into human erythrocytes by Plasmodium falciparum.
abstract: The Apicomplexan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invades human erythrocytes through multiple ligand-receptor interactions. Some strains of P. falciparum are sensitive to neuraminidase treatment of the host erythrocyte and these parasites have been termed sialic acid-dependent as they utilize receptors containing sialic acid. In contrast, other strains can efficiently invade neuraminidase-treated erythrocytes and hence are sialic acid-independent. The molecular interactions that allow P. falciparum to differentially utilize receptors for merozoite invasion are not understood. The P. falciparum reticulocyte-binding protein homologue (PfRh or PfRBL) family have been implicated in the invasion process but their exact role is unknown. PfRh1, a member of this protein family, appears to be expressed in all parasite lines analysed but there are marked differences in the level of expression between different strains. We have used targeted gene disruption of the PfRh1 gene in P. falciparum to show that the encoded protein is required for sialic acid-dependent invasion of human erythrocytes. The DeltaPfRh1 parasites are able to invade normally; however, they utilize a pattern of ligand-receptor interactions that are more neuraminidase-resistant. Current data suggest a strategy based on the differential function of specific PfRh proteins has evolved to allow P. falciparum parasites to utilize alternative receptors on the erythrocyte surface for evasion of receptor polymorphisms and the host immune system.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Triglia
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
authors.forename: Robert T
authors.initials: RT
authors.lastname: Good
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D004912:Erythrocytes / Q000737:chemistry / Q000469:parasitology*; D017353:Gene Deletion; D018390:Gene Targeting; D017125:Genes, Protozoan; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology
chemical_list: D008024:Ligands; D015800:Protozoan Proteins; C503374:RH1 protein, Plasmodium falciparum; D037521:Virulence Factors; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid