恶性疟原虫毒性蛋白PfEMP1的作用与运输

受恶性疟原虫感染的宿主红细胞会进行细胞重建,其中最明显的改变就是受染红细胞表面出现很多疣状突起(knob)。恶性疟红细胞膜相关蛋白1(PfEMP1)是疟原虫产生的毒性蛋白;这种蛋白通过受染红细胞表面的疣状突起被锚定在红细胞表面,介导红细胞与宿主内皮细胞受体结合,从而使恶性疟原虫能够逃避宿主的清除,并因阻塞作用致宿主脏器功能受损。PfEMP1由疟原虫基因组编码产生,通过其自身的一些特殊结构域将PfEMP1输送至包绕恶性疟原虫的纳虫空泡。由于红细胞没有亚细胞器,因此疟原虫必须建立自己的蛋白运输通路方可将虫体蛋白运至宿主细胞表面。受染红细胞胞质出现的茂氏裂褶是一种分泌细胞器,它将毒性蛋白由纳虫空泡运至红细胞膜表面。

恶性疟原虫var基因家族与抗原变异研究进展

恶性疟原虫变异抗原基因(var基因)家族编码的恶性疟原虫红细胞膜蛋白1(PfEMP1)是介导恶性疟原虫抗原变异和红细胞黏附微血管的媒介。本文从恶性疟原虫抗原变异和致病性、感染红细胞表面变异分子的表达、var基因家族的基因结构、PfEMP1蛋白的黏附特性以及var基因家族的变异调控等方面对恶性疟原虫var基因家族与抗原变异的研究进行综述。

Acquisition of naturally acquired antibody response to Plasmodium falciparum erythrocyte membrane protein 1-DBLα and differential regulation of IgG subclasses in severe and uncomplicated malaria

Objectives: To explore whether individuals infected with Plasmodium falciparum(P. falciparum) develop antibodies directed against Pf EMP1-DBLa, and to assess their IgG subclass distribution in severe and uncomplicated malaria.Methods: The anti-PfDBLα IgG and their IgG subclass distributions in plasma of severe(SM) and uncomplicated malaria(UCM) were assessed by enzyme-linked immunoabsorbent assay. The antibody profiles to P. falciparum blood stage antigens were evaluated. CD36 binding ability was determined by static receptor-binding assays.Rosette formation was performed by staining with acridine orange.Results: Significantly higher number of UCM(86.48%) than SM(57.78%) plasma contained total acquisition of specific IgG to P. falciparum antigens(P = 0.000). Similar manners were seen in response to P. falciparum DBLa with significant difference(UCM,59.46% vs SM, 40.00%; P = 0.014). Anti-PfDBLα-IgG1 and-IgG3 were the predominant subclasses. Similar percentage of UCM(31.82%) and SM(33.33%) plasma contained only IgG1, while 13.64% of UCM and 27.78% of SM plasma contained only IgG3. AntiPfDBLα-IgG1 coexpressed with more than one subclass was noted(UCM, 27.27%; SM,16.67%). Obviously, IgG1 coexpressed with IgG3(9.09%) was observed in only UCM plasma. IgG1 was coexpressed with IgG2 in UCM(9.09%) and SM(11.11%) plasma,while IgG1 was coexpressed with IgG4 only in UCM plasma(4.55%). IgG subclasses to P. falciparum antigens were distributed in a similar manner. Only the levels of IgG1, but not IgG3 were significantly higher in UCM than in SM.Conclusions: These data suggest that individuals infected with P. falciparum can develop the anti-Pf EMP1 antibodies with the major contribution of specific IgG subclasses. The balance and the levels of anti-PfDBLα IgG subclasses play a crucial role in antibody mediated protection against severe malaria.

恶性疟原虫红细胞表面膜蛋白1DBLα区不同区段与血型抗原的结合特性分析

根据大肠杆菌密码子组成特点，重新优化并合成FCR3S1．2株恶性疟原虫红细胞表膜蛋白1（PfEMPI）DBLα区基因序列，利用PCR的方法，将优化后的基因序列分为3段。分别将全长基因和3个基因片段在大肠杆菌中表达、纯化。通过重组蛋白与血型抗原的亲和试验，分析功能区与血型抗原是否具有亲和力。结果表明，重组的PfEMPl一DBLα全长蛋白质及分段表达的重组蛋白对血型抗原A、B均有特异性的亲和力。本实验结果为揭示恶性疟原虫的主要致病分子与人体细胞相互作用机制提供了实验依据。