Plasmodium vivax Merozoite Surface Protein-3 (PvMSP3): Expression of an 11 Member Multigene Family in Blood-Stage Parasites
Plasmodium vivax Merozoite Surface Protein-3 (PvMSP3): Expression of an 11 Member Multigene Family in Blood-Stage Parasites
复制标题
DOI：
10.1371/journal.pone.0063888
复制
发表时间：
2013-05-23
期刊：
影响因子：
3.7
通讯作者：
Galinski, Mary R.
中科院分区：
文献类型：
--
作者：
Jiang, Jianlin;Barnwell, John W.;Galinski, Mary R.
背景：间日疟原虫卵裂子表面蛋白-3 （PvMSP3）家族的三个成员（PvMSP3- α、PvMSP3- β和PvMSP3- γ）最初被鉴定，后来被证明是一个更大的高度多样化家族的一部分，由10号染色体上首尾相连的一组基因编码。pvmsp3 - α和pvmsp3 - β已成为流行病学研究中的遗传标记，并正在作为候选疫苗进行评估。本研究探讨了整个家族的基因和蛋白表达及其相关意义。方法/主要发现：研究了间日疟原虫（Salvador 1株）10号染色体上60kb的pvmsp3基因位点，并比较了它们在血期发育过程中的转录、翻译和蛋白定位模式。11个pvmsp3类似序列编码一个n端NLRNG特征基序、一个包含重复可变七肽序列的中心结构域和保守的亲水性c端特征。该位点的另一个ORF缺乏这些特征，因此被排除在家族成员之外。在滋养体和分裂体期RNA中检测到代表所有11个pvmsp3基因的转录本。使用分裂期提取物和每个PvMSP3蛋白特异性抗体的定量免疫印迹表明，除PvMSP3.11外，其他蛋白均可检测到。免疫印迹法还在近缘类人猿种cynomolgi和P. knowlesi中检测到同源物。免疫荧光分析证实，8个PvMSP3s存在于成熟分裂者中。独特的是，PvMSP3.7只在分裂子的顶端表达。结论/意义：在证实为pvmsp3家族成员的11个基因中，检测到代表10个基因表达的特异性蛋白。在分裂子周围可见8个pvmsp3。而PvMSP3.7在分生子的顶端被检测到。Pvmsp3.11转录本存在，但未检测到相应的蛋白。PvMSP3的功能仍然未知。预计10个表达的PvMSP3s在分裂子生物学中具有独特和互补的功能。
Background: Three members of the Plasmodium vivax merozoite surface protein-3 (PvMSP3) family (PvMSP3-alpha, PvMSP3-beta and PvMSP3-gamma) were initially characterized and later shown to be part of a larger highly diverse family, encoded by a cluster of genes arranged head-to-tail in chromosome 10. PvMSP3-alpha and PvMSP3-beta have become genetic markers in epidemiological studies, and are being evaluated as vaccine candidates. This research investigates the gene and protein expression of the entire family and pertinent implications.Methodology/Principal Findings: A 60 kb multigene locus from chromosome 10 in P. vivax (Salvador 1 strain) was studied to classify the number of pvmsp3 genes present, and compare their transcription, translation and protein localization patterns during blood-stage development. Eleven pvmsp3 paralogs encode an N-terminal NLRNG signature motif, a central domain containing repeated variable heptad sequences, and conserved hydrophilic C-terminal features. One additional ORF in the locus lacks these features and was excluded as a member of the family. Transcripts representing all eleven pvmsp3 genes were detected in trophozoite- and schizont-stage RNA. Quantitative immunoblots using schizont-stage extracts and antibodies specific for each PvMSP3 protein demonstrated that all but PvMSP3.11 could be detected. Homologs were also detected by immunoblot in the closely related simian species, P. cynomolgi and P. knowlesi. Immunofluorescence assays confirmed that eight of the PvMSP3s are present in mature schizonts. Uniquely, PvMSP3.7 was expressed exclusively at the apical end of merozoites.Conclusion/Significance: Specific proteins were detected representing the expression of 10 out of 11 genes confirmed as members of the pvmsp3 family. Eight PvMSP3s were visualized surrounding merozoites. In contrast, PvMSP3.7 was detected at the apical end of the merozoites. Pvmsp3.11 transcripts were present, though no corresponding protein was detected. PvMSP3 functions remain unknown. The ten expressed PvMSP3s are predicted to have unique and complementary functions in merozoite biology.