An Invariant Protein That Colocalizes With VAR2CSA on Plasmodium falciparum-Infected Red Cells Binds to Chondroitin Sulfate A.
J Infect Dis
; 225(11): 2011-2022, 2022 06 01.
Article
de En
| MEDLINE
| ID: mdl-34718641
ABSTRACT
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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Paludisme à Plasmodium falciparum
/
Vaccins contre le paludisme
/
Paludisme
Limites:
Female
/
Humans
/
Pregnancy
Langue:
En
Journal:
J Infect Dis
Année:
2022
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique
Pays de publication:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA