Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA
Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA
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DOI：
10.1371/journal.pone.0137695
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发表时间：
2015-09-22
期刊：
影响因子：
3.7
通讯作者：
Ndam, Nicaise Tuikue
中科院分区：
文献类型：
--
作者：
Doritchamou, Justin;Sabbagh, Audrey;Ndam, Nicaise Tuikue
恶性疟原虫VAR2CSA蛋白被转运到感染的红细胞表面并在其上表达，在胎盘性疟疾(PM)中起关键作用。它是目前预防PM的疫苗的主要候选者然而，VAR2CSA的抗原性多态对疫苗的开发构成了挑战。基于对其配体结合N末端区域序列多态性的详细分析，我们评估了感染孕妇的寄生虫分离株的var2csa。结果首次揭示了在功能关键的N-末端ID1结构域中存在主要的二型区。表达VAR2CSA的寄生虫分离株具有该结构域中的特定基序，与妊娠和寄生虫密度相关的效应有关。这些观察结果对指导目前正在开发的基于VAR2CSA的疫苗的优化工作特别感兴趣。
The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence of a major dimorphic region in the functionally critical N-terminal ID1 domain. Parasite isolates expressing VAR2CSA with particular motifs present within this domain are associated with gravidity-and parasite density-related effects. These observations are of particular interest in guiding efforts with respect to optimization of the VAR2CSA-based vaccines currently under development.