title: Highly co-ordinated var gene expression and switching in clinical Plasmodium falciparum isolates from non-immune malaria patients.
abstract: Antigenic variation to fool the immune system is one of the molecular tricks Plasmodium uses to maintain infection in its human host. The exclusive expression of the surface-exposed PfEMP1 molecules, encoded by var genes, is the best example for this. Central questions regarding the dynamics of antigenic variation, namely the rate of switching and the regulation of var gene expression in Plasmodium falciparum, are yet unanswered. To elucidate the in vivo situation, we studied var gene switching by analysing the var transcripts from parasites isolated from 20 non-immune malaria patients as well as during subsequent in vitro generations. Parasites were found to be highly co-ordinated as the whole population isolated from individual patients usually expressed only one dominant - preferentially group A -var gene. While some isolates have very low switching rates, others switched their var gene expression in every generation. However, during extended cultivation the co-ordinated expression and switching is lost resulting in random expression of all var gene groups. Switching as observed on the RNA level was also supported on the protein level using PfEMP1-specific antibodies. The results suggest that var genes switch in an ordered, hierarchical manner at much higher rates than previously described.
authors: Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Anna
authors: A
authors: Bachmann
authors: Sabine
authors: S
authors: Predehl
authors: Jürgen
authors: J
authors: May
authors: Simone
authors: S
authors: Harder
authors: Gerd D
authors: GD
authors: Burchard
authors: Tim-Wolf
authors: TW
authors: Gilberger
authors: Egbert
authors: E
authors: Tannich
authors: Iris
authors: I
authors: Bruchhaus
mesh_terms: D000818:Animals; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000382:microbiology*; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum