Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains

TY - JOUR

T1 - Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains

AU - Jespersen, Jakob S

AU - Wang, Christian W

AU - Mkumbaye, Sixbert I

AU - Minja, Daniel Tr

AU - Petersen, Bent

AU - Turner, Louise

AU - Petersen, Jens Ev

AU - Lusingu, John Pa

AU - Theander, Thor G

AU - Lavstsen, Thomas

N1 - © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRα1-EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction.

AB - Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRα1-EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction.

U2 - 10.15252/emmm.201606188

DO - 10.15252/emmm.201606188

M3 - Journal article

C2 - 27354391

SN - 1757-4676

VL - 8

SP - 839

EP - 850

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

IS - 8

ER -