TARGETED GENE DISRUPTION SHOWS THAT KNOBS ENABLE MALARIA-INFECTED RED-CELLS TO CYTOADHERE UNDER PHYSIOLOGICAL SHEAR-STRESS

Knobs at the surface of erythrocytes infected with Plasmodium falcipar um have been proposed to be important in adherence of these cells to t he vascular endothelium. This structure contains the knob-associated h istidine-rich protein (KAHRP) and the adhesion receptor P. falciparum erythrocyte membrane protein 1. We have disrupted the gene encoding KA HRP and show that it is essential for knob formation. Knob transfectan ts adhere to CD36 in static assays; when tested under flow conditions that mimic those of postcapillary venules, however, the binding to CD3 6 was dramatically reduced. These data suggest that knobs on P. falcip arum-infected erythrocytes exert an important influence on adherence o f parasitized-erythrocytes to microvascular endothelium, an important process in the pathogenesis of P. falciparum infections.