title: Plasmodium falciparum variant surface antigen expression patterns during malaria.
abstract: The variant surface antigens expressed on Plasmodium falciparum-infected erythrocytes are potentially important targets of immunity to malaria and are encoded, at least in part, by a family of var genes, about 60 of which are present within every parasite genome. Here we use semi-conserved regions within short var gene sequence "tags" to make direct comparisons of var gene expression in 12 clinical parasite isolates from Kenyan children. A total of 1,746 var clones were sequenced from genomic and cDNA and assigned to one of six sequence groups using specific sequence features. The results show the following. (1) The relative numbers of genomic clones falling in each of the sequence groups was similar between parasite isolates and corresponded well with the numbers of genes found in the genome of a single, fully sequenced parasite isolate. In contrast, the relative numbers of cDNA clones falling in each group varied considerably between isolates. (2) Expression of sequences belonging to a relatively conserved group was negatively associated with the repertoire of variant surface antigen antibodies carried by the infected child at the time of disease, whereas expression of sequences belonging to another group was associated with the parasite "rosetting" phenotype, a well established virulence determinant. Our results suggest that information on the state of the host-parasite relationship in vivo can be provided by measurements of the differential expression of different var groups, and need only be defined by short stretches of sequence data.
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom. pbull@kilifi.mimcom.net
authors.forename: Peter C
authors.initials: PC
authors.lastname: Bull
authors.forename: Matthew
authors.initials: M
authors.lastname: Berriman
authors.forename: Sue
authors.initials: S
authors.lastname: Kyes
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Neil
authors.initials: N
authors.lastname: Hall
authors.forename: Moses M
authors.initials: MM
authors.lastname: Kortok
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Chris I
authors.initials: CI
authors.lastname: Newbold
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology; D002648:Child; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum