Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains
Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains
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DOI：
10.15252/emmm.201606188
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发表时间：
2016-08-01
影响因子：
11.1
通讯作者：
Laystsen, Thomas
中科院分区：
文献类型：
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作者：
Jespersen, Jakob S.;Wang, Christian W.;Laystsen, Thomas
最严重的恶性疟原虫感染是幼儿经历的。表达特定多态性恶性疟原虫红细胞膜蛋白 1 (PfEMP1) 粘附分子子集的寄生虫的血管隔离会引发严重症状。最近，通过某些 PfEMP1 的 CIDR α 1 结构域结合人内皮蛋白 C 受体 (EPCR) 的寄生虫与儿童严重疟疾有关。然而，目前尚不清楚 EPCR 结合 CIDR α 1 结构域在多大程度上体现了严重疟疾中表达的 PfEMP1。在这里，我们对严重疟疾儿童中主导 var 转录组的近全长转录本进行了表征，发现编码的 PfEMP1 的唯一共同特征是 CIDR α 1 结构域。这些基因在患有严重疟疾贫血和脑型疟疾的儿童中高度显性表达。这些观察结果支持了这样的假设：CIDR α1-EPCR 相互作用是严重疟疾发病机制的关键，并强化了寻求旨在抑制或减少这种相互作用的破坏性影响的疫苗或辅助治疗的基本原理。
Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDR alpha 1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDR alpha 1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDR alpha 1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDR alpha 1-EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction.