A single member of the Plasmodium falciparum var multigene family determines cytoadhesion to the placental receptor chondroitin sulphate A.
In high-transmission regions, protective clinical immunity to Plasmodium falciparum develops during the early years of life, limiting serious complications of malaria in young children. Pregnant women are an exception and are especially susceptible to severe P. falciparum infections resulting from the massive adhesion of parasitized erythrocytes to chondroitin sulphate A (CSA) present on placental syncytiotrophoblasts. Epidemiological studies strongly support the feasibility of an intervention strategy to protect pregnant women from disease. However, different parasite molecules have been associated with adhesion to CSA. In this work, we show that disruption of the var2csa gene of P. falciparum results in the inability of parasites to recover the CSA-binding phenotype. This gene is a member of the var multigene family and was previously shown to be composed of domains that mediate binding to CSA. Our results show the central role of var2CSA in CSA adhesion and support var2CSA as a leading vaccine candidate aimed at protecting pregnant women and their fetuses.
Viebig
Nicola K
NK
Unité de Biologie des Interactions Hôte-Parasite, CNRS URA 2581, Institut Pasteur, Paris, France.
Gamain
Benoit
B
Scheidig
Christine
C
Lépolard
Catherine
C
Przyborski
Jude
J
Lanzer
Michael
M
Gysin
Jürg
J
Scherf
Artur
A
D000818:Animals; D000913:Antibodies, Protozoan; D000940:Antigenic Variation; D015152:Blotting, Northern; D015139:Blotting, Southern; D018955:CD36 Antigens / Q000096:biosynthesis / Q000378:metabolism; D002448:Cell Adhesion; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003001:Cloning, Molecular; D003434:Crossing Over, Genetic; D005091:Exons; D005260:Female; D016678:Genome; D018503:Genome, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000635:transmission; D008954:Models, Biological; D008957:Models, Genetic; D005810:Multigene Family; D009154:Mutation; D010641:Phenotype; D010920:Placenta / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics; D012313:RNA / Q000378:metabolism; D013997:Time Factors; D014327:Trophoblasts / Q000378:metabolism
D000913:Antibodies, Protozoan; D018955:CD36 Antigens; D015800:Protozoan Proteins; D012313:RNA; D002809:Chondroitin Sulfates