Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes.
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.
Jensen
Anja T R
AT
Department of Medical Microbiology and Immunology, The Panum Institute, Building 24-2, Blegdamsvej 3, 2200 Copenhagen, Denmark. atrj@biobase.dk
Magistrado
Pamela
P
Sharp
Sarah
S
Joergensen
Louise
L
Lavstsen
Thomas
T
Chiucchiuini
Antonella
A
Salanti
Ali
A
Vestergaard
Lasse S
LS
Lusingu
John P
JP
Hermsen
Rob
R
Sauerwein
Robert
R
Christensen
Jesper
J
Nielsen
Morten A
MA
Hviid
Lars
L
Sutherland
Colin
C
Staalsoe
Trine
T
Theander
Thor G
TG
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D003001:Cloning, Molecular; D017931:DNA Primers; D004910:Erythrocyte Membrane / Q000469:parasitology; D005786:Gene Expression Regulation / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000503:physiopathology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction / Q000379:methods; D015800:Protozoan Proteins / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000235:genetics
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017931:DNA Primers; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum