Abstract
BackgroundAdhesin proteins are used by Plasmodium parasites to bind and invade target cells. Hence, characterising molecules that participate in reticulocyte interaction is key to understanding the molecular basis of Plasmodium vivax invasion. This study focused on predicting functionally restricted regions of the P. vivax GPI-anchored micronemal antigen (PvGAMA) and characterising their reticulocyte binding activity.ResultsThe pvgama gene was initially found in P. vivax VCG-I strain schizonts. According to the genetic diversity analysis, PvGAMA displayed a size polymorphism very common for antigenic P. vivax proteins. Two regions along the antigen sequence were highly conserved among species, having a negative natural selection signal. Interestingly, these regions revealed a functional role regarding preferential target cell adhesion.ConclusionsTo our knowledge, this study describes PvGAMA reticulocyte binding properties for the first time. Conserved functional regions were predicted according to natural selection analysis and their binding ability was confirmed. These findings support the notion that PvGAMA may have an important role in P. vivax merozoite adhesion to its target cells.
Highlights
Adhesin proteins are used by Plasmodium parasites to bind and invade target cells
Synonymous divergence was greater than non-synonymous divergence (P < 0.0001) when comparing pvgama sequences to each related species: KN-KS P. vivax/P. cynomolgi = -0.041 (0.006); KN-KS P. vivax/P. inui = -0.062 (0.008); KN-KS P. vivax/P. fragile = -0.030 (0.006); KN-KS P. vivax/P. knowlesi = -0.072 (0.009); KN-KS P. vivax/P. coatneyi = -0.049 (0.007)
308 negatively-selected codons were observed amongst species (Fig. 1); a lot of them were in the conserved regions
Summary
Adhesin proteins are used by Plasmodium parasites to bind and invade target cells. characterising molecules that participate in reticulocyte interaction is key to understanding the molecular basis of Plasmodium vivax invasion. Current efforts to develop an anti-malarial vaccine have mainly focused on P. falciparum, given the availability of robust in vitro culturing techniques for this parasite (currently unavailable for P. vivax) which has led to a large-scale identification of genes [5], transcripts [6] and proteins [7]. This information has led to an improved understanding of the molecules involved in P. falciparum merozoite invasion of erythrocytes. Plasmodium falciparum GAMA (PfGAMA) binds to human erythrocytes, an interaction
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