Two alleles of the 175-kilodalton Plasmodium falciparum erythrocyte binding antigen

Abstract

EHA-175, erythrocyte binding antigen 175, is a 175-kDa antigen of Plasmodium [alciparum which has been shown to be involved in the recognition of erythrocytes by merozoites and may be involved in the process of erythrocyte invasion. Invasion of erythrocytes by Camp strain merozoites is inhibited by pre-treatment of red blood cells by EBA-175 from the heterologous strain, FCR-3. The sequence of the Camp strain has been published and we report here the sequence of the FCR-3 strain. The sequences are nearly identical except for a 423-bp segment in the FCR-3 strain, F-scgmcnt. that is not found in the Camp strain and a 342-bp segment, C-segment, present in the Camp strain but not in the FCR-3 strain. The locations of these two segments are different in Camp and FCR-3 EBA-175 genes and there is little DNA or amino acid sequence homology between them. The essentially dimorphic alleles, F-segment and C-segment, are conserved in all isolates examined to date. Evidence of genetic cross-over between the FCR-3 and the Camp EBA-175 genes was not observed in the analysis of a limited number of wild isolates. The continued study of the biological relevance of these sequence divergences in EBA-17S may further elucidate the sequence of events resulting in merozoite invasion of erythrocytes.

Imbalanced Distribution of Plasmodium falciparum EBA-175 Genotypes Related to Clinical Status in Children from Bakoumba, Gabon

“…These cysteine-rich segments, F1 and F2, are responsible for glycophorin A binding to the erythrocyte membrane 4 and contain a very small number of polymorphic regions. EBA-175 region III is located in the central part of the gene, and genomic studies of two P. falciparum strains revealed two highly dimorphic segments in region III,8,9 Dimorphism is referred to as the F-fragment in the FCR-3 strain and the C-fragment in the CAMP strain. The two segments are inserted at different positions of region III and differ in length by 27 amino acids.…”

“…EBA-175 region III is located in the central part of the gene, and genomic studies of two P. falciparum strains revealed two highly dimorphic segments in region III, named FCR-3 and CAMP. 5,8,9 Dimorphism is referred to as the F-fragment in the FCR-3 strain and the C-fragment in the CAMP strain. The two segments are inserted at different positions of region III and differ in length by 27 amino acids.…”

Far from the Madding Crowd: the Molecular Basis for Immunological Escape ofPlasmodium falciparum

“…However, this region is specifically dimorphic and no functional role has yet been identified for it (Ware et al, 1993;Healer et al, 2013;Persson et al, 2013).…”

Evolution of allelic dimorphism in malarial surface antigens

“…That is, a locus should not be considered dimorphic if there is more than one-fourth as much within-class as between-class divergence. The utility of this metric is illustrated by the analysis of two P. falciparum antigens, EBA-175 and MSP-3, which have been reported to exhibit allelic dimorphism (Ware et al, 1993;Conway and Baum, 2002) but do not pass the one-fourth rule (Supplementary Material online).…”

“…Such dimorphic lineages of alleles are present in the genes coding for P. falciparum merozoite surface proteins MSP-1 (Tanabe et al, 1987;Miller et al, 1993) and MSP-2 (Snewin et al, 1991;Ferreira and Hartl, 2006) (Figure 1). They have also been suggested to occur in MSP-3 (McColl and Anders, 1997) and MSP-6 (Pearce et al, 2004) (Figure 1), and EBA-175, a 175-kDa parasite molecule that binds to sialic acid and glycophorin A during red blood cell invasion (Ware et al, 1993). The Msp-1 locus of P. vivax also comprises highly divergent and presumably ancient alleles (Putaporntip et al, 2006).…”