Open AccessPlasmodium falciparum var genes expressed in children with severe malaria encode CIDR α1 domains
Author(s) -
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
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201606188
Subject(s) - parasitology , medical microbiology , clinical microbiology , tanzania , malaria , library science , medicine , family medicine , biology , virology , history , immunology , microbiology and biotechnology , pathology , ethnology , computer science
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 (Pf EMP 1) adhesion molecules. Parasites binding human endothelial protein C receptor ( EPCR ) through the CIDR α1 domain of certain Pf EMP 1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR ‐binding CIDR α1 domains epitomize Pf EMP 1 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 Pf EMP 1 was CIDR α1 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 CIDR α1‐ 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.