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

Jakob S. Jespersen, Christian W. Wang, Sixbert I. Mkumbaye, Daniel T R Minja, Bent Petersen, Louise Turner, Jens E. V. Petersen, John P. A. Lusingu, Thor G. Theander, Thomas Lavstsen

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    Abstract

    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.
    Original languageEnglish
    JournalEMBO Molecular Medicine
    Volume8
    Issue number7
    Pages (from-to)685-829
    Number of pages12
    ISSN1757-4676
    DOIs
    Publication statusPublished - 2016

    Bibliographical note

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Keywords

    • CIDR
    • EPCR
    • PfEMP1
    • Severe childhood malaria
    • var

    Cite this

    Jespersen, J. S., Wang, C. W., Mkumbaye, S. I., Minja, D. T. R., Petersen, B., Turner, L., Petersen, J. E. V., Lusingu, J. P. A., Theander, T. G., & Lavstsen, T. (2016). Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains. EMBO Molecular Medicine, 8(7), 685-829. https://doi.org/10.15252/emmm.201606188