Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains
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Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains. / Jespersen, Jakob S; Wang, Christian W; Mkumbaye, Sixbert I; Minja, Daniel Tr; Petersen, Bent; Turner, Louise; Petersen, Jens Ev; Lusingu, John Pa; Theander, Thor G; Lavstsen, Thomas.
In: EMBO Molecular Medicine, Vol. 8, No. 8, 2016, p. 839-850.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2016
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
VL - 8
SP - 839
EP - 850
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 8
ER -
ID: 164414380