Malaria Parasite Ligands And Host Cell Receptors

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

1. P. vivax malaria was long thought to require the Duffy antigen receptor (DARC) for erythrocyte invasion. The recent discovery of DARC-negative infections, however, suggests an alternative pathway. We investigated this by expressing the Duffy Binding-Like (DBL) domain of the P. vivax erythrocyte binding protein (PvEBP). We confirmed this domain binds to both DARC-positive and DARC-negative cells. Through a screening process, we identified Complement Receptor 1 (CR1) as the receptor for PvEBP. CR1, which is also a known receptor for a Plasmodium falciparum malaria parasite, was found to be the exclusive binding partner for PvEBP. Furthermore, our findings show that a specific subdomain of CR1, the Long Homology Repeat A (LHR-A), is responsible for this interaction. Building on these findings, we are leading research to demonstrate that the Plasmodium vivax Erythrocyte Binding Protein (EBP) is a key factor in the invasion of Duffy-negative red blood cells, a discovery with significant implications for vaccine development. 2. Post-translational modification of proteins in malaria parasites with N-, O-, and C-linked glycans is limited but functionally significant. Glycosylphosphatidylinositols (GPIs) are the most common glycans, and the modification of proteins with these anchors is essential for parasite survival. GPI-anchored proteins (GPI-APs) are critical for all life cycle stages, including parasite development, egress, motility, and host cell adhesion and invasion. This review summarizes the current understanding of the structure and function of these glycan moieties, which has important implications for developing new antimalarial drugs and vaccines.