Genetic Polymorphism of Plasmodium vivax msp1p, a Paralog of Merozoite Surface Protein 1, from Worldwide Isolates

Abstract

Plasmodium vivax msp1p, a paralog of the candidate vaccine antigen P. vivax merozoite surface protein 1, possesses a signal peptide at its N-terminus and two epidermal growth factor–like domains at its C-terminus with a glycosylphosphatidylinositol attachment site. The msp1p gene locus may have originated by a duplication of the msp1 gene locus in a common ancestor of the analyzed Plasmodium species and lost from P. yoelii, P. berghei, and P. falciparum during their evolutionary history. Full-length sequences of the msp1p gene were generally highly conserved; they had a few amino acid substitutions, one highly polymorphic E/Q-rich region, and a single-to-triple hepta-peptide repeat motif. Twenty-one distinguishable allelic types (A1–A21) of the E/Q-rich region were identified from worldwide isolates. Among them, four types were detected in isolates from South Korea. The length polymorphism of the E/Q-rich region might be useful as a genetic marker for population structure studies in malaria-endemic areas.

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

“…The surface-exposed antigens on merozoites are abundant and serve essential functions that mediate initial contact with erythrocyte surface. This hypothesis was supported by previous functional studies of P. vivax merozoite surface proteins [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] and Plasmodium falciparum (15,16). Recently, PvMSP1 paralog (PvMSP1P) was reported as a novel erythrocyte binding protein (17).…”

“…PvMSP1P is similar to PvMSP1 in terms of its amino acid sequence, with conservation of 12 cysteine residues in its epidermal growth factor (EGF)-like domains in the C-terminal region. Moreover, these cysteine residues were also shown to be highly conserved not only in P. vivax merozoite surface antigens (PvMSP1, PvMSP8, and PvMSP10) but also in the surface proteins of diverse humaninvasive Plasmodium species (18,19). Although the human EGF domain was shown to be related to dendritic cell maturation and T cell activation (20), the functions of the EGF-like domain in Plasmodium spp.…”

The Plasmodium vivax Merozoite Surface Protein 1 Paralog Is a Novel Erythrocyte-Binding Ligand of P. vivax

“…1B). We have described in our previous report that Pvmsp1p protein is encoded by a single exon gene and comprises a signal peptide (aa 1 to 28), GPI-anchor (aa 1834 to 1854), E/Q-rich region (aa 1157 to 1172), heptapeptide tandem repeat region (aa 905 to 918), and a transmembrane domain (aa 1832 to 1854) (26). The predicted molecular masses of PfMSP-1, PvMSP-1, and PvMSP1P are similar, approximately 200 kDa.…”

“…The commonality between PvMSP1 and PvMSP1P in their primary structural features, and their stage-specific expression profile, led us to speculate that PvMSP1P might be a member of the PvMSPs. However, PvMSP1P has a limited number of polymorphisms in comparison with PvMSPs and is highly conserved, including the C terminus that contains the EGF-like domains (26), suggesting that the function of PvMSP1P-19 is important during parasite invasion of erythrocytes. Although PvMSP1 and PvMSP1P are expressed on the surface of merozoite, transcriptome analysis of blood-stage vivax parasites (PlasmoDB) shows that PvMSP1 is highly upregulated in the schizont-stage parasite; however, expression of PvMSP1P is only moderately upregulated, suggesting that the role of PvMSP1P may be different from that of PvMSP1 (37).…”

“…Antibodies against the C terminus of PvMSP1 in P. vivax-immune humans and immunized animals play a major role in the parasite inhibitory response (15,22,25). The paralog of pvmsp1, named pvmsp1p (PVX_099975), is highly conserved among worldwide isolates (26). The primary structure of PvMSP1P contains a putative GPI anchor attachment signal and double epidermal growth factor (EGF)-like domains at the C terminus.…”