Characterization of a Plasmodium falciparum PHISTc protein, PF3D7_0801000, in blood- stage malaria parasites

Characterization of a Plasmodium falciparum PHISTc protein, PF3D7_0801000, in blood- stage malaria parasites
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血期疟疾寄生虫中恶性疟原虫 PHISTc 蛋白 PF3D7_0801000 的表征

DOI:
10.1016/j.parint.2020.102240
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发表时间:
2021
影响因子:
1.9
通讯作者:
Takashima Eizo
Takashima Eizo
中科院分区:
医学3区
文献类型:
--
作者:
Nagaoka Hikaru;Kanoi Bernard N.;Morita Masayuki;Nakata Takahiro;Palacpac Nirianne M.Q.;Egwang Thomas G.;Horii Toshihiro;Tsuboi Takafumi;Takashima Eizo

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在红细胞内发育过程中,恶性疟原虫利用多种蛋白质支持红细胞入侵、细胞内生长发育以及宿主免疫逃避。由于这些蛋白是寄生虫在红细胞内存活和繁殖的关键,它们是抗疟疾疫苗的有吸引力的靶点。在这项研究中,我们试图表征PHISTC家族的一个成员,PF3D7_0801000,作为潜在的疫苗靶点。利用小麦胚芽无细胞系统表达了pF3D7_0801000(G93-L494,pF3D7_0801000N)的N-末端片段,并制备了特异性免疫血清。我们观察到PF3D7_0801000定位于裂殖子,而抗PF3D7_0801000N的抗体对P有一定的抑制作用。恶性寄生虫在体外培养中的生长。对编码序列的滑动窗口分析表明,pf3d7_0801000在非洲寄生虫分离株中相对保守。在接触疟疾的乌干达人群中的抗体图谱显示,随着抗体获得量的增加,PF3D7_0801000N具有强烈的免疫反应。综上所述,这些发现提示有必要进一步评估PF3D7_0801000在裂殖子入侵中的作用以及作为无性血液期疫苗候选抗原的实用性。
During intraerythrocytic development Plasmodium falciparum deploys numerous proteins to support erythrocyte invasion, intracellular growth and development, as well as host immune evasion. Since these proteins are key for parasite intraerythrocytic survival and propagation, they represent attractive targets for antimalarial vaccines. In this study we sought to characterize a member of the PHISTc family of proteins, PF3D7_0801000, as a potential vaccine target. Using the wheat germ cell-free system we expressed the N-terminal region of PF3D7_0801000 (G93-L494, PF3D7_0801000N) and generated specific immune sera. We observed that PF3D7_0801000 localizes in merozoites, and antibodies against PF3D7_0801000N modestly inhibitP. falciparumparasite growth inin vitroculture. Sliding window analysis of the coding sequence revealed thatpf3d7_0801000nis relatively conserved among African parasite isolates. Antibody profiles in a malaria-exposed Ugandan population revealed that PF3D7_0801000N is strongly immunoreactive with antibody acquisition increasing with age. Taken together, these findings suggest the need for further evaluation of PF3D7_0801000 for its role in merozoite invasion and utility as an asexual blood-stage vaccine candidate antigen.