Malaria's deadly grip: cytoadhesion of P lasmodium falciparum ‐infected erythrocytes

Summary Cytoadhesion of P lasmodium falciparum ‐infected erythrocytes to host microvasculature is a key virulence determinant. Parasite binding is mediated by a large family of clonally variant adhesion proteins, termed P . falciparum erythrocyte membrane protein 1 ( PfEMP 1), encoded by var genes and expressed at the infected erythrocyte surface. Although PfEMP 1 proteins have extensively diverged under opposing selection pressure to maintain ligand binding while avoiding antibody‐mediated detection, recent work has revealed they can be classified into different groups based on chromosome location and domain composition. This grouping reflects functional specialization of PfEMP 1 proteins for different human host and microvascular binding niches and appears to be maintained by gene recombination hierarchies. Inone extreme, a specific PfEMP 1 variant is associated with placental binding and malaria during pregnancy, while other PfEMP 1 subtypes appear to be specialized for infection of malaria naïve hosts. Here, we discuss recent findings on the origins and evolution of the var gene family, the structure–function of PfEMP 1 proteins, and a distinct subset of PfEMP 1 variants that have been associated with severe childhood malaria.