An Invariant Protein That Colocalizes With VAR2CSA on Plasmodium falciparum-Infected Red Cells Binds to Chondroitin Sulfate A

J Infect Dis. 2022 Jun 1;225(11):2011-2022. doi: 10.1093/infdis/jiab550.


Background: Plasmodium falciparum-infected red blood cells (iRBCs) bind and sequester in deep vascular beds, causing malaria-related disease and death. In pregnant women, VAR2CSA binds to chondroitin sulfate A (CSA) and mediates placental sequestration, making it the major placental malaria (PM) vaccine target.

Methods: In this study, we characterize an invariant protein associated with PM called P falciparum chondroitin sulfate A ligand (PfCSA-L).

Results: Recombinant PfCSA-L binds both placental CSA and VAR2CSA with nanomolar affinity, and it is coexpressed on the iRBC surface with VAR2CSA. Unlike VAR2CSA, which is anchored by a transmembrane domain, PfCSA-L is peripherally associated with the outer surface of knobs through high-affinity protein-protein interactions with VAR2CSA. This suggests that iRBC sequestration involves complexes of invariant and variant surface proteins, allowing parasites to maintain both diversity and function at the iRBC surface.

Conclusions: The PfCSA-L is a promising target for intervention because it is well conserved, exposed on infected cells, and expressed and localized with VAR2CSA.

Keywords: Plasmodium falciparum; invariant protein; placental malaria; sequestration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Chondroitin Sulfates
  • Erythrocytes / parasitology
  • Female
  • Humans
  • Malaria Vaccines*
  • Malaria* / prevention & control
  • Malaria, Falciparum* / parasitology
  • Placenta / parasitology
  • Plasmodium falciparum
  • Pregnancy


  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Malaria Vaccines
  • Chondroitin Sulfates