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Limited global diversity of the Plasmodium vivax merozoite surface protein 4 gene

机译:间日疟原虫裂殖子表面蛋白4基因的有限全球多样性

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摘要

Merozoite surface proteins (MSPs) of the malaria parasites are major candidates for vaccine development targeting asexual blood stages. However, the diverse antigenic repertoire of these antigens that induce strain-specific protective immunity in human is a major challenge for vaccine design and often determines the efficacy of a vaccine. Here we further assessed the genetic diversity of Plasmodium vivax MSP4 (PvMSP4) protein using 195 parasite samples collected mostly from Thailand, Indonesia and Brazil. Overall, PvMSP4 is highly conserved with only eight amino acid substitutions. The majority of the haplotype diversity was restricted to the two short tetrapeptide repeat arrays in exon 1 and 2, respectively. Selection and neutrality tests indicated that exon 1 and the entire coding region of PvMSP4 were under purifying selection. Despite the limited nucleotide polymorphism of PvMSP4, significant genetic differentiation among the three major parasite populations was detected. Moreover, microgeographical heterogeneity was also evident in the parasite populations from different endemic areas of Thailand.
机译:疟原虫的裂殖子表面蛋白(MSP)是针对无性血液阶段的疫苗开发的主要候选对象。然而,这些抗原的多种抗原库在人体内诱导了菌株特异性的保护性免疫,这是疫苗设计的主要挑战,并且常常决定疫苗的功效。在这里,我们使用195个主要来自泰国,印度尼西亚和巴西的寄生虫样本进一步评估了间日疟原虫MSP4(PvMSP4)蛋白的遗传多样性。总体而言,PvMSP4是高度保守的,只有八个氨基酸取代。大多数单倍型多样性分别限于外显子1和2中的两个短的四肽重复序列。选择和中性测试表明外显子1和PvMSP4的整个编码区正在纯化选择中。尽管PvMSP4的核苷酸多态性有限,但在三个主要的寄生虫种群中检测到显着的遗传分化。此外,在泰国不同流行地区的寄生虫种群中,微观地理异质性也很明显。

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