Abstract
Plasmodium parasites’ invasion of their target cells is a complex, multi-step process involving many protein-protein interactions. Little is known about how complex the interaction with target cells is in Plasmodium vivax and few surface molecules related to reticulocytes’ adhesion have been described to date. Natural selection, functional and structural analysis were carried out on the previously described vaccine candidate P. vivax merozoite surface protein 10 (PvMSP10) for evaluating its role during initial contact with target cells. It has been shown here that the recombinant carboxyl terminal region (rPvMSP10-C) bound to adult human reticulocytes but not to normocytes, as validated by two different protein-cell interaction assays. Particularly interesting was the fact that two 20-residue-long regions (388DKEECRCRANYMPDDSVDYF407 and 415KDCSKENGNCDVNAECSIDK434) were able to inhibit rPvMSP10-C binding to reticulocytes and rosette formation using enriched target cells. These peptides were derived from PvMSP10 epidermal growth factor (EGF)-like domains (precisely, from a well-defined electrostatic zone) and consisted of regions having the potential of being B- or T-cell epitopes. These findings provide evidence, for the first time, about the fragments governing PvMSP10 binding to its target cells, thus highlighting the importance of studying them for inclusion in a P. vivax antimalarial vaccine.
Highlights
The results showed that limited msp10 diversity (π = 0.0012) is a worldwide feature (Supplementary data 1), seeming to be due to natural selection
Potential regions involved in parasite-host interaction were defined by inferring codons under negative selection as not all protein sequences might be involved in parasite-host interaction and given that functionally important regions are conserved by purifying selection
PvMSP10 human reticulocyte bindingunknown activity considering this and focusedinto on account evaluating human reticulocyte binding considering contact, this and taking thePvMSP10 importance of molecules involved inactivity initial parasite-cell taking into account importance involved in initial contact, the in silico findingsthe reported for theofP.molecules vivax msp10 gene [11,12]
Summary
Many studies to date have been related to surface molecules participating in early Plasmodium falciparum merozoite (Mrz) adhesion to red blood cells (RBC) [1]. Studying proteins related to Plasmodium vivax Mrz adhesion or invasion has been difficult since it has not been possible to continuously propagate this parasite in vitro, given its preference for invading reticulocytes (cells occurring in low percentages in different sources) [2] for which high percentages cannot be obtained and needing to be totally viable for supplementing cultures. Several P. vivax Mrz surface proteins’ (merozoite surface protein 1 (MSP1), MSP1 paralogue (MSP1-P), reticulocyte binding surface protein (RBSA) and tryptophanrich antigen (TRAgs)) binding to human RBC has been studied experimentally via different approaches.
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