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

TY - JOUR

T1 - Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes

AU - Jensen, Anja T R

AU - Magistrado, Pamela

AU - Sharp, Sarah

AU - Joergensen, Louise

AU - Lavstsen, Thomas

AU - Chiucchiuini, Antonella

AU - Salanti, Ali

AU - Vestergaard, Lasse S

AU - Lusingu, John P

AU - Hermsen, Rob

AU - Sauerwein, Robert

AU - Christensen, Jesper

AU - Nielsen, Morten A

AU - Hviid, Lars

AU - Sutherland, Colin

AU - Staalsoe, Trine

AU - Theander, Thor G

N1 - 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

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20040274

DO - 10.1084/jem.20040274

M3 - Journal article

C2 - 15123742

SN - 0022-1007

VL - 199

SP - 1179

EP - 1190

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 9

ER -