Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand.
Sci Rep. 2020 Jul 3;10(1):10977. doi: 10.1038/s41598-020-67222-z.
Plasmodium vivax merozoite surface protein 3 (PvMSP3) is encoded by a multi-gene family. Of these, PvMSP3α, PvMSP3β and PvMSP3γ, are considered to be vaccine targets. Despite comprehensive analyses of PvMSP3α and PvMSP3β, little is known about structural and sequence diversity in PvMSP3γ. Analysis of 118 complete pvmsp3γ sequences from diverse endemic areas of Thailand and 9 reported sequences has shown 86 distinct haplotypes. Based on variation in insert domains, pvmsp3γ can be classified into 3 types, i.e. Belem, Salvador I and NR520. Imperfect nucleotide repeats were found in six regions of the gene; none encoded tandem amino acid repeats. Predicted coiled-coil heptad repeats were abundant in the protein and displayed variation in length and location. Interspersed phase shifts occurred in the heptad arrays that may have an impact on protein structure. Polymorphism in pvmsp3γ seems to be generated by intragenic recombination and driven by natural selection. Most P. vivax isolates in Thailand exhibit population structure, suggesting limited gene flow across endemic areas. Phylogenetic analysis has suggested that insert domains could have been subsequently acquired during the evolution of pvmsp3γ. Sequence and structural diversity of PvMSP3γ may complicate vaccine design due to alteration in predicted immunogenic epitopes among variants.
恶性疟原虫裂殖子表面蛋白 3（PvMSP3）由一个多基因家族编码。其中，PvMSP3α、PvMSP3β和 PvMSP3γ被认为是疫苗靶点。尽管对 PvMSP3α 和 PvMSP3β 进行了全面分析，但对 PvMSP3γ 的结构和序列多样性知之甚少。对来自泰国不同流行地区的 118 个完整的 pvmsp3γ 序列和 9 个报告序列进行分析表明，存在 86 个不同的单倍型。根据插入结构域的变异，pvmsp3γ 可分为 3 种类型，即 Belem、Salvador I 和 NR520。在基因的 6 个区域发现了不完全的核苷酸重复序列；没有编码串联氨基酸重复序列。预测的卷曲螺旋七肽重复序列在该蛋白中丰富，长度和位置存在差异。在七肽重复序列中发生了交错的相位变化，这可能会影响蛋白质结构。pvmsp3γ 的多态性似乎是由基因内重组产生的，并受到自然选择的驱动。泰国的大多数恶性疟原虫分离株表现出种群结构，表明流行地区之间的基因流有限。系统发育分析表明，插入结构域可能是在 pvmsp3γ 的进化过程中获得的。由于变体之间预测的免疫原性表位发生改变，PvMSP3γ 的序列和结构多样性可能会使疫苗设计复杂化。
