Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes.

Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes.
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与严重的儿童疟疾相关的恶性疟原虫优先表达由A组VAR基因编码的PFEMP1。

DOI:
10.1084/jem.20040274
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发表时间:
2004-05-03
影响因子:
15.3
通讯作者:
Theander, TG
Theander, TG
中科院分区:
医学1区
文献类型:
--
作者:
Jensen, ATR;Magistrado, P;Sharp, S;Joergensen, L;Lavstsen, T;Chiucciuini, A;Salanti, A;Vestergaard, LS;Lusingu, JP;Hermsen, R;Sauerwein, R;Christensen, J;Nielsen, MA;Hviid, L;Sutherland, C;Staalsoe, T;Theander, TG

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寄生虫编码的变体表面抗原(VSA)如var基因编码的恶性疟原虫红细胞膜蛋白1(PfEMP 1)家族负责恶性疟原虫疟疾中的抗原变异和感染的红细胞(RBC)细胞粘附。在非免疫患者中引起严重疟疾的寄生虫倾向于表达VSA的限制性子集(VSASM),其不同于与无并发症疟疾和无症状感染相关的VSA(VSAUM)。我们比较了表达VSAUM的恶性疟原虫克隆3D 7与表达VSASM的体外选择的亚系中的var基因转录,以鉴定负责VSASM表型的PfEMP 1。VSASM的表达伴随着A组var基因的上调。最显著上调的A组基因(PFD 1235 w/MAL7P1.1)被翻译成在感染的RBC表面上表达的蛋白质。由A组var基因编码的蛋白质,如PFD 1235 w/MAL7P1.1,似乎参与严重疾病的发病机制,因此是针对危及生命的恶性疟原虫疟疾的疫苗的有吸引力的候选者。
Parasite-encoded variant surface antigens (VSAs) like the var gene–encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSASM) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSAUM). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSAUM to in vitro–selected sublines expressing VSASM to identify PfEMP1 responsible for the VSASM phenotype. Expression of VSASM was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.
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