title: Differential var gene transcription in Plasmodium falciparum isolates from patients with cerebral malaria compared to hyperparasitaemia.
abstract: The Plasmodium falciparum variant erythrocyte surface antigens known as PfEMP1, encoded by the var gene family, are thought to play a crucial role in malaria pathogenesis because they mediate adhesion to host cells and immuno-modulation. Var genes have been divided into three major groups (A, B and C) and two intermediate groups (B/A and B/C) on the basis of their genomic location and upstream sequence. We analysed expressed sequence tags of the var gene DBLalpha domain to investigate var gene transcription in relation to disease severity in Malian children. We found that P. falciparum isolates from children with cerebral malaria (unrousable coma) predominantly transcribe var genes with DBLalpha1-like domains that are characteristic of Group A or B/A var genes. In contrast, isolates from children with equally high parasite burdens but no symptoms or signs of severe malaria (hyperparasitaemia patients) predominantly transcribe var genes with DBLalpha0-like domains that are characteristic of the B and C-related var gene groups. These results suggest that var genes with DBLalpha1-like domains (Group A or B/A) may be implicated in the pathogenesis of cerebral malaria, while var genes with DBLalpha0-like domains promote less virulent malaria infections.
authors.affiliation: Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Kyriacou
authors.forename: Graham N
authors.initials: GN
authors.lastname: Stone
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Challis
authors.forename: Ahmed
authors.initials: A
authors.lastname: Raza
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Lyke
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Abdoulaye K
authors.initials: AK
authors.lastname: Koné
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
authors.forename: J Alexandra
authors.initials: JA
authors.lastname: Rowe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002675:Child, Preschool; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000235:genetics / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000469:parasitology*; D008969:Molecular Sequence Data; D018512:Parasitemia / Q000235:genetics / Q000469:parasitology; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum