Jensen Anja T R, Magistrado Pamela, Sharp Sarah, Joergensen Louise, Lavstsen Thomas, Chiucchiuini Antonella, Salanti Ali, Vestergaard Lasse S, Lusingu John P, Hermsen Rob, Sauerwein Robert, Christensen Jesper, Nielsen Morten A, Hviid Lars, Sutherland Colin, Staalsoe Trine, Theander Thor G
Department of Medical Microbiology and Immunology, The Panum Institute, Building 24-2, Blegdamsvej 3, 2200 Copenhagen, Denmark.
J Exp Med. 2004 May 3;199(9):1179-90. doi: 10.1084/jem.20040274.
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 (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) 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.
诸如由var基因编码的恶性疟原虫红细胞膜蛋白1（PfEMP1）家族等寄生虫编码的可变表面抗原（VSA），在恶性疟原虫疟疾中负责抗原变异和感染红细胞（RBC）的细胞黏附。在非免疫患者中引起严重疟疾的寄生虫倾向于表达VSA的一个受限子集（VSA(SM)），其不同于与无并发症疟疾和无症状感染相关的VSA（VSA(UM)）。我们将表达VSA(UM)的未选择的恶性疟原虫克隆3D7中的var基因转录与表达VSA(SM)的体外选择亚系中的var基因转录进行比较，以鉴定负责VSA(SM)表型的PfEMP1。VSA(SM)的表达伴随着A组var基因的上调。上调最显著的A组基因（PFD1235w/MAL7P1.1）被翻译成在感染的RBC表面表达的一种蛋白质。A组var基因编码的蛋白质，如PFD1235w/MAL7P1.1，似乎参与了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疫苗的有吸引力的候选物。
