Abstract
Merozoite surface protein 7 (MSP-7) is a multigene family expressed during malaria blood-stage infection. MSP-7 forms complex with MSP-1 prior to merozoite egress from erythrocytes, and could affect merozoite invasion of erythrocytes. To characterize sequence variation in the orthologue in P. vivax (PvMSP-7), a gene member encoding PvMSP-7E was analyzed among 92 Thai isolates collected from 3 major endemic areas of Thailand (Northwest: Tak, Northeast: Ubon Ratchathani, and South: Yala and Narathiwat provinces). In total, 52 distinct haplotypes were found to circulate in these areas. Although population structure based on this locus was observed between each endemic area, no genetic differentiation occurred between populations collected from different periods in the same endemic area, suggesting spatial but not temporal genetic variation. Sequence microheterogeneity in both N- and C- terminal regions was predicted to display 4 and 6 α-helical domains, respectively. Signals of purifying selection were observed in α-helices II-X, suggesting structural or functional constraint in these domains. By contrast, α-helix-I spanning the putative signal peptide was under positive selection, in which amino acid substitutions could alter predicted CD4+ T helper cell epitopes. The central region of PvMSP-7E comprised the 5’-trimorphic and the 3’-dimorphic subregions. Positive selection was identified in the 3’ dimorphic subregion of the central domain. A consensus of intrinsically unstructured or disordered protein was predicted to encompass the entire central domain that contained a number of putative B cell epitopes and putative protein binding regions. Evidences of intragenic recombination were more common in the central region than the remainders of the gene. These results suggest that the extent of sequence variation, recombination events and selective pressures in the PvMSP-7E locus seem to be differentially affected by protein secondary structure.
Highlights
In most malaria endemic areas outside of Africa, Plasmodium vivax mainly coexists with Plasmodium falciparum, both of which affect global health burden and contribute remarkably to economic loss [1, 2]
merozoite surface protein-1 (MSP-1) has been considered a prime target for asexual blood stage vaccine development, recent studies have shown that other merozoite surface proteins, such as merozoite surface proteins-6 and -7 (MSP-6 and Merozoite surface protein 7 (MSP-7)), form a non-covalent complex with MSP-1 prior to receptor-ligand recognition [7,8,9,10]
A consensus for P. falciparum subtilisin 1 (PfSUB1) cleavage site seems to be present in PvMSP7E (S4 Fig) [43]
Summary
In most malaria endemic areas outside of Africa, Plasmodium vivax mainly coexists with Plasmodium falciparum, both of which affect global health burden and contribute remarkably to economic loss [1, 2]. One of the prime strategies for asexual blood stage vaccine development is to mount immunity that interrupts the invasion of Plasmodium merozoites into erythrocytes [5]. MSP-1 has been considered a prime target for asexual blood stage vaccine development, recent studies have shown that other merozoite surface proteins, such as merozoite surface proteins-6 and -7 (MSP-6 and MSP-7), form a non-covalent complex with MSP-1 prior to receptor-ligand recognition [7,8,9,10]. Disruption of P. falciparum MSP-7 (PfMSP-7) has resulted in partial impairment in erythrocyte invasion by malarial merozoites [11]. Specific binding of P. berghei MSP-7 to P-selectin has suggested the role of this protein in modulating disease severity through immunological process [14]. Immunity induced by vaccines derived from malarial MSP-7 could potentially interrupt parasite development
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