title: Molecular analysis of erythrocyte invasion in Plasmodium falciparum isolates from Senegal.
abstract: The human malaria parasite, Plasmodium falciparum, utilizes multiple ligand-receptor interactions for the invasion of human erythrocytes. Members of the reticulocyte binding protein homolog (PfRh) family have been shown to be critical for directing parasites to alternative erythrocyte receptors that define invasion pathways. Recent studies have identified gene amplification, sequence polymorphism, and variant expression of PfRh paralogs as mechanisms underlying discrimination between pathways for invasion. In this study, we find considerable heterogeneity in the invasion profiles of clonal, uncultured P. falciparum parasite isolates from a low-transmission area in Senegal. Molecular analyses revealed minimal variation in protein expression levels of the PfRh ligands, PfRh1, PfRh2a, and PfRh2b, and an absence of gene amplification in these isolates. However, significant sequence polymorphism was found within repeat regions of PfRh1, PfRh2a, and PfRh2b. Furthermore, we identified a large sequence deletion ( approximately 0.58 kb) in the C-terminal region of the PfRh2b gene at a high prevalence in this population. In contrast to findings of earlier studies, we found no associations between specific sequence variants and distinct invasion pathways. Overall these data highlight the importance of region-specific elaborations in PfRh sequence and expression polymorphisms, which has important implications in our understanding of how the malaria parasite responds to polymorphisms in erythrocyte receptors and/or evades the immune system.
authors.affiliation: Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Cameron V
authors.initials: CV
authors.lastname: Jennings
authors.forename: Ambroise D
authors.initials: AD
authors.lastname: Ahouidi
authors.forename: Martine
authors.initials: M
authors.lastname: Zilversmit
authors.forename: Amy K
authors.initials: AK
authors.lastname: Bei
authors.forename: Julian
authors.initials: J
authors.lastname: Rayner
authors.forename: Ousmane
authors.initials: O
authors.lastname: Sarr
authors.forename: Omar
authors.initials: O
authors.lastname: Ndir
authors.forename: Dyann F
authors.initials: DF
authors.lastname: Wirth
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004912:Erythrocytes / Q000469:parasitology*; D014644:Genetic Variation; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000302:isolation & purification / Q000472:pathogenicity*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D012675:Senegal
chemical_list: D015800:Protozoan Proteins; C503374:RH1 protein, Plasmodium falciparum