Highly co-ordinated var gene expression and switching in clinical Plasmodium falciparum isolates from non-immune malaria patients.

TY - JOUR

T1 - Highly co-ordinated var gene expression and switching in clinical Plasmodium falciparum isolates from non-immune malaria patients.

AU - Bachmann, Anna

AU - Predehl, Sabine

AU - May, Jürgen

AU - Harder, Simone

AU - Burchard, Gerd-Dieter

AU - Gilberger, Tim-Wolf

AU - Tannich, Egbert

AU - Bruchhaus, Iris

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Genotype

KW - Phylogeny

KW - Polymerase Chain Reaction

KW - Malaria, Falciparum/microbiology

KW - Plasmodium falciparum/classification/genetics/pathogenicity

KW - Protozoan Proteins/genetics

KW - Animals

KW - Humans

KW - Genotype

KW - Phylogeny

KW - Polymerase Chain Reaction

KW - Malaria, Falciparum/microbiology

KW - Plasmodium falciparum/classification/genetics/pathogenicity

KW - Protozoan Proteins/genetics

M3 - SCORING: Journal article

VL - 13

SP - 1397

EP - 1409

JO - CELL MICROBIOL

JF - CELL MICROBIOL

SN - 1462-5814

IS - 9

M1 - 9

ER -