title: Variation in Plasmodium falciparum erythrocyte invasion phenotypes and merozoite ligand gene expression across different populations in areas of malaria endemicity.
abstract: Plasmodium falciparum merozoites use diverse alternative erythrocyte receptors for invasion and variably express cognate ligands encoded by the erythrocyte binding antigen (eba) and reticulocyte binding-like homologue (Rh) gene families. Previous analyses conducted on parasites from single populations in areas of endemicity revealed a wide spectrum of invasion phenotypes and expression profiles, although comparisons across studies have been limited by the use of different protocols. For direct comparisons within and among populations, clinical isolates from three different West African sites of endemicity (in Ghana, Guinea, and Senegal) were cryopreserved and cultured ex vivo after thawing in a single laboratory to assay invasion of target erythrocytes pretreated with enzymes affecting receptor subsets. Complete invasion assay data from 67 isolates showed no differences among the populations in the broad range of phenotypes measured by neuraminidase treatment (overall mean, 40.6% inhibition) or trypsin treatment (overall mean, 83.3% inhibition). The effects of chymotrypsin treatment (overall mean, 79.2% inhibition) showed heterogeneity across populations (Kruskall-Wallis P = 0.023), although the full phenotypic range was seen in each. Schizont-stage transcript data for a panel of 8 invasion ligand genes (eba175, eba140, eba181, Rh1, Rh2a, Rh2b, Rh4, and Rh5) were obtained for 37 isolates, showing similar ranges of variation in each population except that eba175 levels tended to be higher in parasites from Ghana than in those from Senegal (whereas levels of eba181 and Rh2b were lower in parasites from Ghana). The broad diversity in invasion phenotypes and gene expression seen within each local population, with minimal differences among them, is consistent with a hypothesis of immune selection maintaining parasite variation.
authors: Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Paul W
authors: PW
authors: Bowyer
authors: Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Lindsay B
authors: LB
authors: Stewart
authors: Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Harvey
authors: H
authors: Aspeling-Jones
authors: Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Ghana.
authors: Henrietta E
authors: HE
authors: Mensah-Brown
authors: Le Dantec Hospital, Universite Cheikh Anta Diop, Dakar, Senegal.
authors: Ambroise D
authors: AD
authors: Ahouidi
authors: Medical Research Council Unit, Fajara, Banjul, The Gambia.
authors: Alfred
authors: A
authors: Amambua-Ngwa
authors: Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Ghana.
authors: Gordon A
authors: GA
authors: Awandare
authors: Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, United Kingdom david.conway@lshtm.ac.uk.
authors: David J
authors: DJ
authors: Conway
mesh_terms: D002648:Child; D002675:Child, Preschool; D019353:Endemic Diseases; D004912:Erythrocytes / Q000469:parasitology*; D005786:Gene Expression Regulation; D005869:Ghana / Q000453:epidemiology; D016701:Guinea / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology*; D052940:Merozoites / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000502:physiology*; D012675:Senegal / Q000453:epidemiology