Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes
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- Plasmodium falciparum associated with severe childhood malaria preferentially expressess PfEMP1 encoded by group A var genes
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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.
Original language | English |
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Journal | Journal of Experimental Medicine |
Volume | 199 |
Issue number | 9 |
Pages (from-to) | 1179-90 |
Number of pages | 11 |
ISSN | 0022-1007 |
DOIs | |
Publication status | Published - 2004 |
Bibliographical note
Keywords: Amino Acid Sequence; Animals; Antibodies, Protozoan; Antigens, Protozoan; Base Sequence; Child; Cloning, Molecular; DNA Primers; Erythrocyte Membrane; Gene Expression Regulation; Genes, Protozoan; Humans; Malaria, Falciparum; Molecular Sequence Data; Plasmodium falciparum; Polymerase Chain Reaction; Protozoan Proteins; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Transcription, Genetic
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