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2017 ; 85
(10
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels
Defining a Dominant Plasmodium falciparum Invasion Pathway into Human
Erythrocytes
#MMPMID28760933
Dankwa S
; Chaand M
; Kanjee U
; Jiang RHY
; Nobre LV
; Goldberg JM
; Bei AK
; Moechtar MA
; Grüring C
; Ahouidi AD
; Ndiaye D
; Dieye TN
; Mboup S
; Weekes MP
; Duraisingh MT
Infect Immun
2017[Oct]; 85
(10
): ä PMID28760933
show ga
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.