Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativit
Author: ["Alexander G. Maier","Manoj T. Duraisingh","John C. Reeder","Sheral S. Patel","James W. Kazura","Peter A. Zimmerman","Alan F. Cowman"]
Publication: Nature Medicine
CITE.CC academic search helps you expand the influence of your papers.
Abstract
Geographic overlap between malaria and the occurrence of mutant hemoglobin and erythrocyte surface proteins has indicated that polymorphisms in human genes have been selected by severe malaria1,2. Deletion of exon 3 in the glycophorin C gene (called GYPCΔex3 here) has been found in Melanesians; this alteration changes the serologic phenotype of the Gerbich (Ge) blood group system, resulting in Ge negativity3,4. The GYPCΔex3 allele reaches a high frequency (46.5%) in coastal areas of Papua New Guinea where malaria is hyperendemic5. The Plasmodium falciparum erythrocyte-binding antigen 140 (EBA140, also known as BAEBL)6,7,8 binds with high affinity to the surface of human erythrocytes. Here we show that the receptor for EBA140 is glycophorin C (GYPC) and that this interaction mediates a principal P. falciparum invasion pathway into human erythrocytes. EBA140 does not bind to GYPC in Ge-negative erythrocytes, nor can P. falciparum invade such cells using this invasion pathway. This provides compelling evidence that Ge negativity has arisen in Melanesian populations through natural selection by severe malaria.
Cite this article
Maier, A., Duraisingh, M., Reeder, J. et al. Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations. Nat Med 9, 87–92 (2003). https://doi.org/10.1038/nm807
