Plasmodium falciparum variant surface antigen expression patterns during malaria.
Plasmodium falciparum variant surface antigen expression patterns during malaria.
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DOI：
10.1371/journal.ppat.0010026
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发表时间：
2005-11
期刊：
影响因子：
6.7
通讯作者：
Newbold CI
中科院分区：
文献类型：
--
作者：
Bull PC;Berriman M;Kyes S;Quail MA;Hall N;Kortok MM;Marsh K;Newbold CI
感染恶性疟原虫的红细胞上表达的变异表面抗原是疟疾免疫的潜在重要目标，并且至少部分地由 var 基因家族编码，其中大约 60 个基因存在于每个寄生虫基因组中。在这里，我们使用短 var 基因序列“标签”内的半保守区域来直接比较来自肯尼亚儿童的 12 种临床寄生虫分离株的 var 基因表达。从基因组和 cDNA 中对总共 1,746 个 var 克隆进行了测序，并使用特定的序列特征分配到六个序列组之一。结果显示如下。 (1) 每个序列组中的基因组克隆的相对数量在寄生虫分离株之间是相似的，并且与单个、完全测序的寄生虫分离株的基因组中发现的基因数量很好地对应。相反，各组中 cDNA 克隆的相对数量在分离株之间差异很大。 (2) 属于相对保守群体的序列表达与受感染儿童在患病时携带的变异表面抗原抗体库呈负相关，而属于另一群体的序列表达与寄生虫“玫瑰花结”表型相关，这是一种公认的毒力决定因素。我们的结果表明，体内宿主-寄生虫关系状态的信息可以通过测量不同var组的差异表达来提供，并且只需要通过短序列数据来定义。在疟疾流行地区长大的人学会了携带疟疾感染而不会患病，这一事实支持了开发疟疾疫苗的希望。令人惊讶的是，人们对于这种免疫力是如何形成的仍然知之甚少。目前的许多研究都集中在宿主如何对暴露于宿主免疫系统的寄生虫抗原产生免疫反应。此类抗原的一个主要家族被插入寄生虫感染的红细胞表面，在那里它们进行抗原转换以逃避正在发生的抗体反应。这些蛋白质由大约 60 个 var 基因组成的家族编码，每个寄生虫基因组中都存在这些基因的变体。 var 基因的极端多样性阻碍了对其在临床分离株中的表达进行有意义的比较。然而，本文的作者表明，var 基因可以放置在作者从肯尼亚儿童收集的所有寄生虫的基因组中具有相似代表性的组中。作者在基因组水平上证明了潜在的相似性，表明不同患者之间的 var 表达模式存在显着差异。特定 var 基因组的表达水平与儿童中发育不良的抗体反应和已确定的寄生虫毒力表型相关。这项研究提供了探索宿主和寄生虫在免疫力发展过程中如何相互适应的工具。
The variant surface antigens expressed on Plasmodium falciparum–infected erythrocytes are potentially important targets of immunity to malaria and are encoded, at least in part, by a family of var genes, about 60 of which are present within every parasite genome. Here we use semi-conserved regions within short var gene sequence “tags” to make direct comparisons of var gene expression in 12 clinical parasite isolates from Kenyan children. A total of 1,746 var clones were sequenced from genomic and cDNA and assigned to one of six sequence groups using specific sequence features. The results show the following. (1) The relative numbers of genomic clones falling in each of the sequence groups was similar between parasite isolates and corresponded well with the numbers of genes found in the genome of a single, fully sequenced parasite isolate. In contrast, the relative numbers of cDNA clones falling in each group varied considerably between isolates. (2) Expression of sequences belonging to a relatively conserved group was negatively associated with the repertoire of variant surface antigen antibodies carried by the infected child at the time of disease, whereas expression of sequences belonging to another group was associated with the parasite “rosetting” phenotype, a well established virulence determinant. Our results suggest that information on the state of the host–parasite relationship in vivo can be provided by measurements of the differential expression of different var groups, and need only be defined by short stretches of sequence data. Hope that it will be possible to develop a malaria vaccine is supported by the fact that individuals who have grown up in malaria endemic regions learn to carry malarial infections without suffering disease. Surprisingly little is still known about how this immunity develops. Much current research focuses on how the host develops immune responses to parasite antigens that are exposed to the host immune system. A major family of such antigens are inserted into the surface of parasite-infected erythrocytes, where they undergo antigenic switching to evade a developing antibody response. These proteins are encoded by a family of approximately 60 var genes, variants of which are present in every parasite genome. The extreme diversity of the var genes has prevented meaningful comparison of their expression in clinical isolates. However, the authors of this paper show that var genes can be placed in groups that have a similar representation in the genomes of all parasites that the authors collected from Kenyan children. Having demonstrated an underlying similarity at the genomic level, the authors show that the var expression patterns vary markedly between different patients. The expression levels of specific groups of var genes was associated with poorly developed antibody responses in the children and a well-established parasite virulence phenotype. The study provides tools for exploring how host and parasite adapt to one another as immunity develops.
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