VAR2CSA is the principal ligand for chondroitin sulfate A in two allogeneic isolates of Plasmodium falciparum
VAR2CSA is the principal ligand for chondroitin sulfate A in two allogeneic isolates of Plasmodium falciparum
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DOI：
10.1016/j.molbiopara.2006.03.006
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发表时间：
2006-08-01
影响因子：
1.5
通讯作者：
Brown, Graham V.
中科院分区：
文献类型：
--
作者：
Duffy, Michael F.;Maier, Alexander G.;Brown, Graham V.
妊娠期间的疟疾导致严重的疾病，其与胎盘中的恶性疟原虫感染的红细胞的隔离有关，所述红细胞粘附于几种宿主受体，包括硫酸软骨素A（CSA）。与胎盘隔离相关的主要CSA结合配体是由var 2csa基因编码的恶性疟原虫红细胞膜蛋白I（PfEMP 1）。我们破坏了var 2csa基因在两个同种异体寄生虫和消融CSA结合。然而，在一个寄生虫系中，我们能够重新选择与两个var基因（var-CS2和varP）转录相关的牛气管CSA粘附。寄生虫转录部分的var-CS2和varP存在于胎盘的一些感染的妇女，但突变的寄生虫转录的var-CS2和varP被确认的男性和孕妇的血清独立的奇偶校验。这项工作提出了由var-CS2和varP编码的PfEMP 1分子可能是胎盘疟疾的次要贡献者的可能性，但也证实了免疫显性的保守var 2csa PfEMP 1在妊娠相关疟疾中的重要性，并加强了var 2csa作为妊娠特异性疟疾疫苗的情况。(c)2006 Elsevier B. V.保留所有权利。
Malaria during pregnancy causes serious disease that is associated with sequestration in the placenta of Plasmodium falciparum infected erythrocytes that adhere to several host receptors, including chondroitin sulfate A (CSA). The principal CSA binding ligand associated with placental sequestration is the R falciparum erythrocyte membrane protein I (PfEMP1), encoded by the var2csa gene. We disrupted the var2csa gene in two allogeneic parasites and ablated CSA binding. However, in one parasite line we were able to re-select for adhesion to bovine trachea CSA associated with transcription of two var genes, var-CS2 and varP. Parasites transcribing parts of var-CS2 and varP were present in the placentae of some infected women but the mutant parasites that transcribed var-CS2 and varP were recognized by sera from men and pregnant women independent of parity. This work raises the possibility that the PfEMP1 molecules encoded by var-CS2 and varP may be minor contributors to placental malaria but also confirms the importance of the immunodominant, conserved var2csa PfEMP1s in pregnancy associated malaria and strengthens the case for var2csa as a pregnancy-specific malaria vaccine. (c) 2006 Elsevier B.V. All rights reserved.