Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels Defining a Dominant Plasmodium falciparum Invasion Pathway into Human Erythrocytes.
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Authors
Dankwa, Selasi
Chaand, Mudit
Kanjee, Usheer
Jiang, Rays HY
Nobre, Luis V
Goldberg, Jonathan M
Bei, Amy K
Moechtar, Mischka A
Grüring, Christof
Ahouidi, Ambroise D
Ndiaye, Daouda
Dieye, Tandakha N
Mboup, Souleymane
Duraisingh, Manoj T
Publication Date
2017-10Journal Title
Infect Immun
ISSN
0019-9567
Publisher
American Society for Microbiology
Volume
85
Issue
10
Language
eng
Type
Article
Physical Medium
Electronic-Print
Metadata
Show full item recordCitation
Dankwa, S., Chaand, M., Kanjee, U., Jiang, R. H., Nobre, L. V., Goldberg, J. M., Bei, A. K., et al. (2017). Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels Defining a Dominant Plasmodium falciparum Invasion Pathway into Human Erythrocytes.. Infect Immun, 85 (10) https://doi.org/10.1128/IAI.00074-17
Abstract
Plasmodium falciparum, the parasite that causes the deadliest form of malaria, has evolved multiple proteins known as invasion ligands that bind to specific erythrocyte receptors to facilitate invasion of human erythrocytes. The EBA-175/glycophorin A (GPA) and Rh5/basigin ligand-receptor interactions, referred to as invasion pathways, have been the subject of intense study. In this study, we focused on the less-characterized sialic acid-containing receptors glycophorin B (GPB) and glycophorin C (GPC). Through bioinformatic analysis, we identified extensive variation in glycophorin B (GYPB) transcript levels in individuals from Benin, suggesting selection from malaria pressure. To elucidate the importance of the GPB and GPC receptors relative to the well-described EBA-175/GPA invasion pathway, we used an ex vivo erythrocyte culture system to decrease expression of GPA, GPB, or GPC via lentiviral short hairpin RNA transduction of erythroid progenitor cells, with global surface proteomic profiling. We assessed the efficiency of parasite invasion into knockdown cells using a panel of wild-type P. falciparum laboratory strains and invasion ligand knockout lines, as well as P. falciparum Senegalese clinical isolates and a short-term-culture-adapted strain. For this, we optimized an invasion assay suitable for use with small numbers of erythrocytes. We found that all laboratory strains and the majority of field strains tested were dependent on GPB expression level for invasion. The collective data suggest that the GPA and GPB receptors are of greater importance than the GPC receptor, supporting a hierarchy of erythrocyte receptor usage in P. falciparum.
Keywords
Erythrocytes, Humans, Plasmodium falciparum, Receptors, Cell Surface, Ligands, Proteomics, Computational Biology, Protein Binding, Glycophorins
Sponsorship
Wellcome Trust (108070/Z/15/Z)
Identifiers
External DOI: https://doi.org/10.1128/IAI.00074-17
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286030
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
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