title: Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Immunology, The Panum Institute, Building 24-2, Blegdamsvej 3, 2200 Copenhagen, Denmark. atrj@biobase.dk
authors.forename: Anja T R
authors.initials: AT
authors.lastname: Jensen
authors.forename: Pamela
authors.initials: P
authors.lastname: Magistrado
authors.forename: Sarah
authors.initials: S
authors.lastname: Sharp
authors.forename: Louise
authors.initials: L
authors.lastname: Joergensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Lavstsen
authors.forename: Antonella
authors.initials: A
authors.lastname: Chiucchiuini
authors.forename: Ali
authors.initials: A
authors.lastname: Salanti
authors.forename: Lasse S
authors.initials: LS
authors.lastname: Vestergaard
authors.forename: John P
authors.initials: JP
authors.lastname: Lusingu
authors.forename: Rob
authors.initials: R
authors.lastname: Hermsen
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
authors.forename: Jesper
authors.initials: J
authors.lastname: Christensen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Nielsen
authors.forename: Lars
authors.initials: L
authors.lastname: Hviid
authors.forename: Colin
authors.initials: C
authors.lastname: Sutherland
authors.forename: Trine
authors.initials: T
authors.lastname: Staalsoe
authors.forename: Thor G
authors.initials: TG
authors.lastname: Theander
mesh_terms: 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
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017931:DNA Primers; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum