Plasmodium vivax Merozoite Surface Protein 1 Paralog as a Mediator of Parasite Adherence to Reticulocytes

Abstract

parasites preferentially invade reticulocytes in human beings. merozoite surface protein 1 (PvMSP1) and PvMSP1 paralog (PvMSP1P) may have important functions in reticulocyte adherence during invasion. These proteins share similar structures, including the presence of two epidermal growth factor (EGF)-like and glycosylphosphatidylinositol (GPI)-anchored domains at the C terminus. However, there have been no reports concerning the functional activity of PvMSP1P in reticulocyte adherence during invasion. In this study, the ability of PvMSP1P-19 to bind to reticulocytes and normocytes was analyzed. The reticulocyte binding activity of PvMSP1P-19 was 4.0-fold higher than its normocyte binding activity. The binding of PvMSP1P-19 to reticulocytes and normocytes was inhibited in a dose-dependent manner by antibodies from immunized rabbits and by antibodies from vivax parasite-infected patients. Consistently, antibodies against PvMSP1P inhibited parasite invasion during short-term cultivation. Similar to the case for PvDBPII binding activity, PvMSP1P-19 binding activity was reduced in chymotrypsin-treated reticulocytes. However, no significant difference between the binding of PvMSP1P-19 to Duffy-positive and Duffy-negative erythrocytes was found. The minimal binding motif of PvMSP1P-19 was characterized using synthetic peptides. The results showed that the residues at amino acid positions 1791 to 1808 may have an important function in mediating merozoite adherence to reticulocytes. The positively charged residues within the EGF-like domain were shown to constitute a key binding motif. This work presents strong evidence supporting the role of PvMSP1P in host target cell selection and invasion of Duffy-independent pathway in Moreover, PvMSP1P-19-specific antibodies may confer protection against reinvasion.

Low Levels of Polymorphisms and Negative Selection in Plasmodum knowlesi Merozoite Surface Protein 8 in Malaysian Isolates

“…Interestingly, all the 12 cysteine residues within the double EGF domains were conserved within the 43 isolates (including the lab adapted strains) indicating conserved functional activity. This conservation of the 12 cysteine residues was also observed for the C-terminal 19 kDa fragment of PvMSP1P and PkMSP1P [26] and binding activity to reticulocytes in P. vivax have been reported [14,27–29]. Sliding window plot analysis of Tajima’s D across the full-length pkmsp8 gene also indicated most values below 0 indicating purifying selection (Fig.…”

Identification and Characterization of Eimeria tenella Microneme Protein (EtMIC8)

“…Adhesion and invasion processes are key steps for apicomplexan parasites infection ( 21 ). These processes are mediated by a variety of parasite proteins that interact with host cells ( 22 – 24 ). Studies have shown that MICs play an important role in the adhesion and invasion of parasites to host cells due to their multiple adhesion domains.…”

The enigmatic mechanisms by which Plasmodium vivax infects Duffy-negative individuals

“…However, the roles of PvRBP1a and of PvRBP2b-TfR1 have not been evaluated specifically in the invasion of Duffy-negative red blood cells. Recently, P. vivax merozoite surface protein-1 paralog (PvMSP1P) and P. vivax glycosylphosphatidylinositol-anchored micronemal antigen (PvGAMA) were shown to bind to both Duffy-positive and Duffy-negative red blood cells, and antibodies against PvMSP1P blocked the related P. knowlesi invasion in Duffy-positive reticulocytes [78][79][80]. Those results suggest that PvGAMA and PvMSP1P are ligands that could be involved in Duffy-independent reticulocyte invasion pathways, although functional demonstration is still lacking.…”