A subset of Plasmodium falciparum SERA genes are expressed and appear to play an important role in the erythrocytic cycle
A subset of Plasmodium falciparum SERA genes are expressed and appear to play an important role in the erythrocytic cycle
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DOI：
10.1074/jbc.m206974200
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发表时间：
2002-12-06
影响因子：
4.8
通讯作者：
Crabb, BS
中科院分区：
文献类型：
--
作者：
Miller, SK;Good, RT;Crabb, BS
恶性疟原虫丝氨酸重复抗原（SERA）作为控制疟疾的血液阶段疫苗已显示出相当大的希望。一种相关的蛋白质，SERPH，也已经在恶性疟原虫中描述。虽然它们的生物学作用仍然未知，但这两种蛋白质都具有木瓜蛋白酶样蛋白酶结构域，可以为治疗干预提供有吸引力的靶点。基因组测序最近表明，SERA和SERPH是第五和第六个基因，分别在一个集群的8个SERA同源物存在于染色体2。在本文中，这八个基因的表达和功能的相关性和第九个SERA同源物在9号染色体上发现的血液阶段的寄生虫进行了检查。使用逆转录酶-PCR和微阵列的方法，我们证明，而mRNA的所有9个SERA基因的合成晚在红细胞周期中，它是那些基因的中心区域的染色体2簇，在这个时候大幅上调。使用对每种SERA特异的抗体，很明显，SERA 4至-6，可能还有SERA 9，在血液阶段寄生虫中合成。来自疟疾免疫个体的抗体与SERA重组蛋白的反应性表明，SERA 2和SERA 3也至少在一些寄生虫群体中表达。为了检查SERA基因是否是血液阶段生长所必需的，靶向破坏8个染色体2 SERA基因中的每一个。而在簇的外围的基因大多数被破坏（SERA 2和-3和SERA 7和-8），那些在中心区域（SERA 4至-6）不能被破坏。不能破坏SERA 4、-5和-6与它们的表观显性表达一致，并暗示这些基因在维持红细胞周期中的重要作用。
The Plasmodium falciparum serine repeat antigen (SERA) has shown considerable promise as a blood stage vaccine for the control of malaria. A related protein, SERPH, has also been described in P. falciparum. Whereas their biological role remains unknown, both proteins possess papain-like protease domains that may provide attractive targets for therapeutic intervention. Genomic sequencing has recently shown that SERA and SERPH are the fifth and sixth genes, respectively, in a cluster of eight SERA homologues present on chromosome 2. In this paper, the expression and functional relevance of these eight genes and of a ninth SERA homologue found on chromosome 9 were examined in blood stage parasites. Using reverse transcriptase-PCR and microarray approaches, we demonstrate that whereas mRNA to all nine SERA genes is synthesized late in the erythrocytic cycle, it is those genes in the central region of the chromosome 2 cluster that are substantially up-regulated at this time. Using antibodies specific to each SERA, it was apparent that SERA4 to -6, and possibly also SERA9, are synthesized in blood stage parasites. The reactivity of antibodies from malaria-immune individuals with the SERA recombinant proteins suggested that SERA2 and SERA3 are also expressed at least in some parasite populations. To examine whether SERA genes are essential to blood stage growth, each of the eight chromosome 2 SERA genes was targeted for disruption. Whereas genes at the periphery of the cluster were mostly dispensable (SERA2 and -3 and SERA7 and -8), those in the central region (SERA4 to -6) could not be disrupted. The inability to disrupt SERA4, -5, and -6 is consistent with their apparent dominant expression and implies an important role for these genes in maintenance of the erythrocytic cycle.