Plasmodium falciparum Merozoite Invasion Is Inhibited by Antibodies that Target the PfRh2a and b Binding Domains
- Author(s)
- Triglia, T; Chen, L; Lopaticki, S; Dekiwadia, C; Riglar, DT; Hodder, AN; Ralph, SA; Baum, J; Cowman, AF;
- Details
- Publication Year 2011-06,Volume 7,Issue #6,Page e1002075
- Journal Title
- PLOS PATHOGENS
- Publication Type
- Journal Article
- Abstract
- Plasmodium falciparum, the causative agent of the most severe form of malaria in humans invades erythrocytes using multiple ligand-receptor interactions. The P. falciparum reticulocyte binding-like homologue proteins (PfRh or PfRBL) are important for entry of the invasive merozoite form of the parasite into red blood cells. We have analysed two members of this protein family, PfRh2a and PfRh2b, and show they undergo a complex series of proteolytic cleavage events before and during merozoite invasion. We show that PfRh2a undergoes a cleavage event in the transmembrane region during invasion consistent with activity of the membrane associated PfROM4 protease that would result in release of the ectodomain into the supernatant. We also show that PfRh2a and PfRh2b bind to red blood cells and have defined the erythrocyte-binding domain to a 15 kDa region at the N-terminus of each protein. Antibodies to this receptor-binding region block merozoite invasion demonstrating the important function of this domain. This region of PfRh2a and PfRh2b has potential in a combination vaccine with other erythrocyte binding ligands for induction of antibodies that would block a broad range of invasion pathways for P. falciparum into human erythrocytes.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- YOELII ADHESIVE PROTEINS; ERYTHROCYTE INVASION; MALARIA PARASITE; HOST ERYTHROCYTE; RECEPTOR SPECIFICITY; GLYCOPHORIN-C; VIVAX; HOMOLOG; GENE; EXPRESSION
- Research Division(s)
- Infection And Immunity
- Publisher's Version
- https://doi.org/10.1371/journal.ppat.1002075
- Open Access at Publisher's Site
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116812/- Terms of Use/Rights Notice
- Copyright Triglia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creation Date: 2011-06-01 12:00:00