A PLASMODIUM-FALCIPARUM ISOLATE WITH A CHROMOSOME-9 DELETION EXPRESSES A TRYPSIN-RESISTANT CYTOADHERENCE MOLECULE

Sequestration of Plasmodium falciparum infected erythrocytes in the ce rebral circulation is strongly implicated in the pathogenesis of cereb ral malaria. From previous studies it was postulated that genes essent ial for cytoadherence were located on the right arm of chromosome 9 as P. falciparum isolates with a deletion in this region lost the capaci ty to cytoadhere vitro and no longer expressed Plasmodium falciparum e rythrocyte membrane protein-1 (PfEMP-1) on the surface of the infected cells. We have selected a P. falciparum isolate from Papua New guinea for high levels of cytoadherence to human umbilical vein endothelial cells (HUVECs) and have shown that the cloned parasite has several nov el properties related cytoadherence. The cloned parasite adheres to HU VECs, does not bind to melanoma cells, and expresses a surface molecul e with most properties of PfEMP-1, despite a deletion in the right arm of chromosome 9. Interestingly, the surface expressed PfEMP-1 in this strain is resistant to trypsin treatment and infected cells continue to cytoadhere after trypsin digestion at a concentration of 100 mu g m l(-1). The receptor on HUVECs for the cloned parasite lines is a molec ule different from any previously described, as parasitized cells do n ot adhere to soluble intercellular adhesion molecule 1, thrombospondin , vascular cell adhesion molecule 1, E-selectin or P-selectin, nor to CD36. Our work, taken together with the results from previous studies, suggest that the ability of parasites to cytoadhere is encoded in at least two distinct genome locations in the parasite, and the diversity of receptor-ligand interaction is greater than previously described.