A single member of the Plasmodium falciparum var multigene family determines cytoadhesion to the placental receptor chondroitin sulphate A
A single member of the Plasmodium falciparum var multigene family determines cytoadhesion to the placental receptor chondroitin sulphate A
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DOI：
10.1038/sj.embor.7400466
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发表时间：
2005-08-01
期刊：
影响因子：
7.7
通讯作者：
Scherf, A
中科院分区：
文献类型：
--
作者：
Viebig, NK;Gamain, B;Scherf, A
在高传播地区，对恶性疟原虫的保护性临床免疫力在生命的最初几年形成，限制了幼儿患疟疾的严重并发症。孕妇是一个例外，特别容易受到严重的恶性疟原虫感染，这是由于寄生的红细胞大量粘附到胎盘合胞体滋养层上的硫酸软骨素A（CSA）。流行病学研究有力地支持采取干预战略保护孕妇免受疾病侵害的可行性。然而，不同的寄生虫分子与CSA的粘附有关。在这项工作中，我们表明恶性疟原虫var 2csa基因的破坏会导致寄生虫无法恢复CSA结合表型。该基因是var多基因家族的成员，并且先前显示由介导与CSA结合的结构域组成。我们的研究结果显示var2CSA在CSA粘附中的核心作用，并支持var2CSA作为旨在保护孕妇及其胎儿的主要候选疫苗。
In high-transmission regions, protective clinical immunity to Plasmodium falciparum develops during the early years of life, limiting serious complications of malaria in young children. Pregnant women are an exception and are especially susceptible to severe A falciparum infections resulting from the massive adhesion of parasitized erythrocytes to chondroitin sulphate A (CSA) present on placental syncytiotrophoblasts. Epidemiological studies strongly support the feasibility of an intervention strategy to protect pregnant women from disease. However, different parasite molecules have been associated with adhesion to CSA. In this work, we show that disruption of the var2csa gene of A falciparum results in the inability of parasites to recover the CSA-binding phenotype. This gene is a member of the var multigene family and was previously shown to be composed of domains that mediate binding to CSA. Our results show the central role of var2CSA in CSA adhesion and support var2CSA as a leading vaccine candidate aimed at protecting pregnant women and their fetuses.