Variant antigens of Plasmodium falciparum encoded by the var multigenic family are multifunctional macromolecules.

Cytoadhesion of parasitized red blood cells (PRBCs) to vascular endothelial cells (sequestration) and binding of unparasitized RBCs to PRBCs (rosetting) are virulence factors of Plasmodium falciparum, the species responsible for lethal human malaria. Variant antigens involved in both phenomena have been identified as products of the multicopy var gene family. In this review, progress in the understanding of molecular mechanisms of sequestration is summarized, in particular, concerning the structure of var gene products related to specificity of binding to endothelial receptors, and the origin of var gene diversity.