| Autor: |
Keitany, Gladys J, Jenkins, Bethany J, Obiakor, Harold T, Daniel, Shaji, Muehlenbachs, Atis, Semblat, Jean-Philippe, Gamain, Benoit, Doritchamou, Justin Y A, Desai, Sanjay A, MacDonald, Nicholas J, Narum, David L, Morrison, Robert, Saveria, Tracy, Vignali, Marissa, Oleinikov, Andrew V, Fried, Michal, Duffy, Patrick E |
| Předmět: |
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| Zdroj: |
Journal of Infectious Diseases; 6/1/2022, Vol. 225 Issue 11, p2011-2022, 12p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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