Rowe J A, Moulds J M, Newbold C I, Miller L H
Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland 20892, USA.
Nature. 1997 Jul 17;388(6639):292-5. doi: 10.1038/40888.
The factors determining disease severity in malaria are complex and include host polymorphisms, acquired immunity and parasite virulence. Studies in Africa have shown that severe malaria is associated with the ability of erythrocytes infected with the parasite Plasmodium falciparum to bind uninfected erythrocytes and form rosettes. The molecular basis of resetting is not well understood, although a group of low-molecular-mass proteins called rosettins have been described as potential parasite ligands. Infected erythrocytes also bind to endothelial cells, and this interaction is mediated by the parasite-derived variant erythrocyte membrane protein PfEMP1, which is encoded by the var gene family. Here we report that the parasite ligand for rosetting in a P. falciparum clone is PfEMP1, encoded by a specific var gene. We also report that complement-receptor 1 (CR1) on erythrocytes plays a role in the formation of rosettes and that erythrocytes with a common African CR1 polymorphism (S1(a-)) have reduced adhesion to the domain of PfEMP1 that binds normal erythrocytes. Thus we describe a new adhesive function for PfEMP1 and raise the possibility that CR1 polymorphisms in Africans that influence the interaction between erythrocytes and PfEMP1 may protect against severe malaria.
决定疟疾疾病严重程度的因素很复杂，包括宿主基因多态性、获得性免疫和寄生虫毒力。非洲的研究表明，重症疟疾与感染恶性疟原虫的红细胞结合未感染红细胞并形成花结的能力有关。尽管一组称为花结素的低分子量蛋白质已被描述为潜在的寄生虫配体，但花结形成的分子基础仍未完全了解。感染的红细胞还与内皮细胞结合，这种相互作用由寄生虫衍生的可变红细胞膜蛋白PfEMP1介导，该蛋白由var基因家族编码。在这里，我们报告恶性疟原虫克隆中花结形成的寄生虫配体是由特定var基因编码的PfEMP1。我们还报告红细胞上的补体受体1（CR1）在花结形成中起作用，并且具有常见非洲CR1多态性（S1(a -)）的红细胞对PfEMP1与正常红细胞结合结构域的粘附力降低。因此，我们描述了PfEMP1的一种新的粘附功能，并提出非洲人影响红细胞与PfEMP1之间相互作用的CR1多态性可能预防重症疟疾的可能性。
