Identification of multiple chondroitin sulfate A (CSA)-binding domains in the var2CSA gene transcribed in CSA-binding parasites.
نویسندگان
چکیده
Malaria in pregnancy is a serious complication associated with parasitized erythrocyte (PE) sequestration in the placenta. Recent work suggests that var genes could play an important role in PE binding to chondroitin sulfate A (CSA), a primary placental adherence receptor. Here, we confirm that var2CSA is transcriptionally up-regulated in CSA-binding parasites and define CSA-binding domains in var2CSA. The identification of multiple binding domains in var2CSA strengthens the evidence for their involvement in malaria during pregnancy and may have applications for the development of a vaccine against malaria in pregnancy.
منابع مشابه
Identification of VAR2CSA domain-specific inhibitory antibodies of the Plasmodium falciparum erythrocyte membrane protein 1 using a novel flow cytometry assay.
VAR2CSA, a member of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, is a leading candidate for use in vaccines to protect first-time mothers from placental malaria (PM). VAR2CSA, which is comprised of a series of six Duffy binding-like (DBL) domains, binds chondroitin sulfate A (CSA) on placental syncytiotrophoblast. Several recombinant DBL domains have been shown to ...
متن کاملDynamics of anti-VAR2CSA immunoglobulin G response in a cohort of senegalese pregnant women.
BACKGROUND Pregnancy-associated malaria (PAM) is precipitated by the accumulation of parasites in the placental intervillous spaces and causes maternal anemia and low birth weight. In PAM, placental parasites adhere to chondroitin sulfate A (CSA) through a unique set of variant surface antigens (VSAPAM). Several studies have shown that 1 var gene, var2csa, is transcribed at high levels and expr...
متن کاملDisruption of Var2csa Gene Impairs Placental Malaria Associated Adhesion Phenotype
Infection with Plasmodium falciparum during pregnancy is one of the major causes of malaria related morbidity and mortality in newborn and mothers. The complications of pregnancy-associated malaria result mainly from massive adhesion of Plasmodium falciparum-infected erythrocytes (IE) to chondroitin sulfate A (CSA) present in the placental intervillous blood spaces. Var2CSA, a member of the P. ...
متن کاملDesigning a VAR2CSA-based vaccine to prevent placental malaria✩
Placental malaria (PM) due to Plasmodium falciparum is a major cause of maternal, fetal and infant mortality, but the mechanisms of pathogenesis and protective immunity are relatively well-understood for this condition, providing a path for vaccine development. P. falciparum parasites bind to chondroitin sulfate A (CSA) to sequester in the placenta, and women become resistant over 1-2 pregnanci...
متن کاملStructural Insight into Epitopes in the Pregnancy-Associated Malaria Protein VAR2CSA
Pregnancy-associated malaria is caused by Plasmodium falciparum malaria parasites binding specifically to chondroitin sulfate A in the placenta. This sequestration of parasites is a major cause of low birth weight in infants and anemia in the mothers. VAR2CSA, a polymorphic multi-domain protein of the PfEMP1 family, is the main parasite ligand for CSA binding, and identification of protective a...
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ورودعنوان ژورنال:
- The Journal of infectious diseases
دوره 191 6 شماره
صفحات -
تاریخ انتشار 2005