P. falciparum expresses proteins on the surface of parasite-infected erythrocytes (IE) helping them bind to an unusually low-sulfated form of chondroitin sulfate A (CSA) in the placental intervillous space. By this process, the parasite avoids being filtered through the spleen where it would be cleared from the bloodstream and killed. When selected in vitro for CSA-binding, the only upregulated gene expressed in the P. falciparum parasites was the var2csa gene. Parasite clones where the var2csa gene was disrupted lost the ability to adhere to CSA by blocking the binding of IE. Its protein, VAR2CSA (Variant Surface antigen 2-CSA), belongs to the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family and contains six Duffy binding-like (DBL) domains. The regions that mediate binding to CSA have not been defined, but DBL2, DBL3, and DBL6 have shown the highest affinity for CSA binding when testing with recombinant single-domains. A unique var gene (PFL0030c or var2csa) encodes this particular PfEMP1, which is differently regulated than other genes from the var family. It is also only expressed as protein in pregnant women, even though the transcript is present in children, men and non-pregnant women. It has a unique regulatory region, a uORF located upstream from the ORF that codes for the VAR2CSA protein. The expression of a protein named PTEF (after Plasmodium falciparum translation-enhancing factor) has been described to be necessary for the translation machinery to overcome the uORF and produce VAR2CSA protein, but the mechanism behind it remains to be elucidated.
Pregnancy-associated malaria
Malaria
Airport malaria
Toxocariasis
Congenital syphilis
Omsk hemorrhagic fever
Congenital malaria
Brain fever