Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria
Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria
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DOI：
10.1046/j.1365-2958.2003.03570.x
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发表时间：
2003-07-01
影响因子：
3.6
通讯作者：
Theander, TG
中科院分区：
文献类型：
--
作者：
Salanti, A;Staalsoe, T;Theander, TG
受感染红细胞（iRBC）的细胞粘附是通过寄生虫编码的克隆变异表面抗原（VSA）介导的，是恶性疟原虫疟疾发病机制的中心过程。妊娠相关疟疾（PAM）与VSA介导的iRBC与胎盘绒毛间隙中的糖胺聚糖硫酸软骨素A（CSA）粘附有关。几项研究指出PfEMP 1 VSA家族的成员是胎盘中CSA特异性iRBC隔离的介质。在这里，我们报告了一个单一的var基因在几个恶性疟原虫分离株选择后，粘附到CSA在体外显着上调。该基因属于一个高度保守和常见的var基因亚家族（var 2csa）。var 2csa基因在结构上不同于寄生虫基因组中的所有其他var基因，缺乏CIDR和DBL-γ结构域。这些结构域先前已涉及PfEMP 1介导的粘附到CD 36和CSA。我们还表明，var 2csa转录在较高的水平，在三个胎盘寄生虫分离物相比，转录从外周血中的两个儿童恶性疟原虫疟疾的寄生虫。因此，该var基因具有预期的编码寄生虫粘附分子的基因的性质，所述寄生虫粘附分子启动与PAM相关的病理。
Cytoadhesion of infected red blood cells (iRBC) is mediated through parasite-encoded, clonally variant surface antigens (VSA) and is a central process in the pathogenesis of Plasmodium falciparum malaria. Pregnancy-associated malaria (PAM) has been linked to VSA-mediated adhesion of iRBC to the glycosaminoglycan chondroitin sulphate A (CSA) in the placental intervillous space. Several studies have pointed to members of the PfEMP1 VSA family as mediators of CSA-specific iRBC sequestration in the placenta. Here, we report marked upregulation of a single var gene in several P. falciparum parasite isolates after selection for adhesion to CSA in vitro . The gene belongs to a highly conserved and common var gene subfamily (var2csa ). The var2csa genes are structurally distinct from all other var genes in the parasite genome in lacking both CIDR and DBL-gamma domains. These domains have previously been implicated in PfEMP1-mediated adhesion to CD36 and CSA. We also show that var2csa was transcribed at higher levels in three placental parasite isolates compared with transcription in parasites from peripheral blood of two children with P. falciparum malaria. This var gene thus has the properties expected of a gene encoding the parasite adhesion molecule that initiates the pathology associated with PAM.