VAR2CSA is the principal ligand for chondroitin sulfate A in two allogeneic isolates of Plasmodium falciparum.
Malaria during pregnancy causes serious disease that is associated with sequestration in the placenta of Plasmodium falciparum infected erythrocytes that adhere to several host receptors, including chondroitin sulfate A (CSA). The principal CSA binding ligand associated with placental sequestration is the P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var2csa gene. We disrupted the var2csa gene in two allogeneic parasites and ablated CSA binding. However, in one parasite line we were able to re-select for adhesion to bovine trachea CSA associated with transcription of two var genes, var-CS2 and varP. Parasites transcribing parts of var-CS2 and varP were present in the placentae of some infected women but the mutant parasites that transcribed var-CS2 and varP were recognized by sera from men and pregnant women independent of parity. This work raises the possibility that the PfEMP1 molecules encoded by var-CS2 and varP may be minor contributors to placental malaria but also confirms the importance of the immunodominant, conserved var2csa PfEMP1s in pregnancy associated malaria and strengthens the case for var2csa as a pregnancy-specific malaria vaccine.
Duffy
Michael F
MF
The Department of Medicine, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Vic. 3050, Australia. mduffy@unimelb.edu.au
Maier
Alexander G
AG
Byrne
Timothy J
TJ
Marty
Allison J
AJ
Elliott
Salenna R
SR
O'Neill
Matthew T
MT
Payne
Paul D
PD
Rogerson
Stephen J
SJ
Cowman
Alan F
AF
Crabb
Brendan S
BS
Brown
Graham V
GV
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D008024:Ligands; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D010920:Placenta / Q000737:chemistry / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000469:parasitology*; D014162:Transfection
D000953:Antigens, Protozoan; D008024:Ligands; D017780:Malaria Vaccines; C512601:VAR2CSA protein, Plasmodium falciparum; D002809:Chondroitin Sulfates