title: Multiple var gene transcripts are expressed in Plasmodium falciparum infected erythrocytes selected for adhesion.
abstract: Adherence of Plasmodium falciparum-infected erythrocytes to the post-capillary endothelium is an important characteristic of malaria infection. The adhesion is mediated predominantly by P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1), a clonally variant protein expressed on the surface of infected red blood cells that appears to be a target of protective immunity. A multi-membered var gene family encodes PfEMP1 and switching expression of different var genes conveys different antigenic and adhesive properties to infected red blood cells. Knowledge about transcriptional control of phenotypic expression, or the mechanisms that allow multiple binding specificities, is very limited. Here, we describe a series of phenotypic selection experiments, which resulted in the expression of different PfEMP1 and the detection of multiple full-length var gene transcripts in the mature trophozoite stage. However, a dominant form of PfEMP1 appeared to be expressed, which suggested that most var transcripts do not lead to a surface expressed PfEMP1 molecule. Parasites bound to specific receptors still expressed multiple full-length var genes and mature trophozoites selected for increased adhesion to a specific receptor retained the ability to bind to multiple receptors. Our findings suggest that a defined adhesive phenotype can be associated with expression of multiple var genes.
authors.affiliation: Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Noviyanti
authors.forename: G V
authors.initials: GV
authors.lastname: Brown
authors.forename: M E
authors.initials: ME
authors.lastname: Wickham
authors.forename: M F
authors.initials: MF
authors.lastname: Duffy
authors.forename: A F
authors.initials: AF
authors.lastname: Cowman
authors.forename: J C
authors.initials: JC
authors.lastname: Reeder
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000469:parasitology / Q000502:physiology / Q000503:physiopathology; D004910:Erythrocyte Membrane / Q000276:immunology / Q000469:parasitology; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology*; D017125:Genes, Protozoan; D014644:Genetic Variation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D018799:Intercellular Adhesion Molecule-1