Effect of var gene disruption on switching in Plasmodium falciparum.
Horrocks P., Pinches R., Kyes S., Kriek N., Lee S., Christodoulou Z., Newbold CI.
The molecular mechanisms underpinning switching of variant antigens on the surface of Plasmodium falciparum-infected erythrocytes are poorly understood. We tested the hypothesis that insertional disruption of the A4var gene, one of two var genes located within the subtelomeric region of one end of chromosome 13, would result in a preferential switch in transcription to the adjacent R29var gene upon rosette selection. In this way, we aimed to mimic the preferential transcription of R29var in rosetting R29 parasites, a parasite line in which the A4var gene is deleted through a chromosome end truncation. Initial analysis of the knock-out parasite lines shows that the insertional disruption of the A4var gene prevents A4 PfEMP1 expression, but that switching transcription to other var gene variants is unaffected. Furthermore, analysis of var transcription in the knock-out parasite line during rosette selection shows that, rather than facilitating a switch to R29var gene transcription, this event was suppressed in the transfectants. These data, and the implications for epigenetic transcriptional control of var genes, are discussed.