Invasion Ligand Diversity and Pathogenesis in Blood‐Stage Malaria

Duraisingh, Manoj T.; Dvorin, Jeffrey D.; Preiser, Peter R.

doi:10.1002/9781118308165.ch19

Cited by 1 publication

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“…that infect humans, P. falciparum is responsible for nearly all deaths and is the only one that undergoes massive IE sequestration in host microvasculature (Smith and Deitsch, ). As homologues of DBL‐EBP erythrocyte invasion ligands are found in human, rodent and primate malaria species (Duraisingh et al ., ), it is likely that this unique cytoadhesion trait evolved from parasite invasion ligands. Although it was originally postulated that P. falciparum was more virulent because it had recently jumped from avian malaria species into humans and was less well adapted (Waters et al ., ), more recent phylogenetic and genome analysis does not support this interpretation and instead suggests that var genes have co‐evolved for a long time with primates.…”

Section: Molecular Mechanisms Of Ie Bindingmentioning

confidence: 99%

Malaria's deadly grip: cytoadhesion ofPlasmodium falciparum-infected erythrocytes

et al. 2013

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Summary Cytoadhesion of Plasmodium 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 (PfEMP1), encoded by var genes and expressed at the infected-erythrocyte surface. Although PfEMP1 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 PfEMP1 proteins for different human host and microvascular binding niches and appears to be maintained by gene recombination hierarchies. In one extreme, a specific PfEMP1 variant is associated with placental binding and malaria during pregnancy, while other PfEMP1 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 PfEMP1 proteins, and a distinct subset of PfEMP1 variants that have been associated with severe childhood malaria.

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Section: Molecular Mechanisms Of Ie Bindingmentioning

confidence: 99%