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.
Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Infect Genet Evol. 2020 Nov;85:104467. doi: 10.1016/j.meegid.2020.104467. Epub 2020 Jul 22.
The merozoite surface protein 9 (MSP9) of malarial parasite forms co-ligand complex with the 19 kDa fragment of merozoite surface protein 1 (MSP1) prior to erythrocyte invasion. Interruption of this process could hamper subsequent asexual erythrocytic development of malaria parasites; therefore, these proteins are considered potential vaccine candidates. In Plasmodium vivax, MSP9 (PvMSP9) contains both conserved and polymorphic repetitive domains that were immunogenic upon natural malaria exposure and conferred protection in vaccination studies in animal models. To investigate the extent of sequence diversity at this locus, 104 P. vivax isolates from 4 major malaria endemic areas of Thailand were analyzed. Results revealed that pvmsp9 contained 3 repeat domains (R1-R3) flanked by conserved domains. Repeat domains exhibit extensive sequence and length variation, in which 14, 39 and 16 haplotypes for domains R1-R3, respectively, circulated in this country. Sequence diversity in pvmsp9 among P. vivax isolates from each endemic area displayed population structure. The extent of sequence diversity in pvmsp9 isolates from the provinces of Tak, Chanthaburi, Ubon Ratchathani and Prachuap Khiri Khan in northwestern, eastern, northeastern and southwestern areas, respectively, was almost comparable and was remarkably higher than that from Yala/Narathiwat population in southern Thailand. Evidence for intragenic recombination in this locus was observed within each P. vivax population except among isolates from Yala and Narathiwat. Synonymous nucleotide diversity significantly exceeded nonsynonymous nucleotide diversity in domains R2 and R3, indicating purifying selection. However, micro-scale signatures of positive and negative selections occurred in both conserved and repeat domains, implying two opposing forces, probably from functional or structural constraint and host immune pressure, could have influenced diversity at this locus. The immunodominant T and B cell epitopes so far identified were invariant or highly conserved across isolates. Further analysis of global isolates is warranted for vaccine design based on this protein.
疟原虫裂殖子表面蛋白 9（MSP9）在入侵红细胞之前与裂殖子表面蛋白 1 的 19kDa 片段形成共配体复合物。阻断这一过程可能会阻碍疟原虫随后的无性红细胞发育；因此，这些蛋白被认为是潜在的疫苗候选物。在间日疟原虫中，MSP9（PvMSP9）包含保守和多态重复结构域，这些结构域在自然疟原虫暴露时具有免疫原性，并在动物模型的疫苗接种研究中提供了保护。为了研究该基因座的序列多样性程度，对来自泰国 4 个主要疟疾流行地区的 104 株间日疟原虫分离株进行了分析。结果表明，pvmsp9 包含 3 个重复结构域（R1-R3），由保守结构域环绕。重复结构域表现出广泛的序列和长度变异，其中 R1-R3 分别有 14、39 和 16 个单倍型循环。来自每个流行地区的间日疟原虫分离株的 pvmsp9 序列多样性显示出种群结构。来自泰国西北部的达府、东部的春武里府、东北部的乌汶府和西南部的巴蜀府的 pvmsp9 分离株的序列多样性几乎相当，明显高于泰国南部也拉府和那拉提瓦府的种群。除了也拉府和那拉提瓦府的分离株外，在每个间日疟原虫种群中都观察到该基因座的基因内重组证据。在 R2 和 R3 结构域中，同义核苷酸多样性显著超过非同义核苷酸多样性，表明存在纯化选择。然而，在保守和重复结构域中都存在正选择和负选择的微观特征，这意味着两种相反的力量，可能来自功能或结构限制和宿主免疫压力，可能影响了该基因座的多样性。迄今为止，已确定的免疫显性 T 细胞和 B 细胞表位在分离株中是不变或高度保守的。基于该蛋白，需要进一步分析全球分离株以进行疫苗设计。
