Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains
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 bindi...
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-06-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201606188 |
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| author | Jakob S Jespersen Christian W Wang Sixbert I Mkumbaye Daniel TR Minja Bent Petersen Louise Turner Jens EV Petersen John PA Lusingu Thor G Theander Thomas Lavstsen |
| author_facet | Jakob S Jespersen Christian W Wang Sixbert I Mkumbaye Daniel TR Minja Bent Petersen Louise Turner Jens EV Petersen John PA Lusingu Thor G Theander Thomas Lavstsen |
| author_sort | Jakob S Jespersen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e6a82f0d8e2c4248ace2a4711a9adad0 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-e6a82f0d8e2c4248ace2a4711a9adad02025-08-20T04:03:06ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-06-018883985010.15252/emmm.201606188Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domainsJakob S Jespersen0Christian W Wang1Sixbert I Mkumbaye2Daniel TR Minja3Bent Petersen4Louise Turner5Jens EV Petersen6John PA Lusingu7Thor G Theander8Thomas Lavstsen9Centre for Medical Parasitology, Department of Immunology & Microbiology, University of CopenhagenCentre for Medical Parasitology, Department of Immunology & Microbiology, University of CopenhagenKilimanjaro Christian Medical University College, Kilimanjaro Clinical Research InstituteNational Institute for Medical Research, Tanga Research CentreCentre for Biological Sequence Analysis, Technical University of DenmarkCentre for Medical Parasitology, Department of Immunology & Microbiology, University of CopenhagenCentre for Medical Parasitology, Department of Immunology & Microbiology, University of CopenhagenCentre for Medical Parasitology, Department of Immunology & Microbiology, University of CopenhagenCentre for Medical Parasitology, Department of Immunology & Microbiology, University of CopenhagenCentre for Medical Parasitology, Department of Immunology & Microbiology, University of CopenhagenAbstract 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.https://doi.org/10.15252/emmm.201606188CIDREPCRPfEMP1severe childhood malariavar |
| spellingShingle | Jakob S Jespersen Christian W Wang Sixbert I Mkumbaye Daniel TR Minja Bent Petersen Louise Turner Jens EV Petersen John PA Lusingu Thor G Theander Thomas Lavstsen Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains EMBO Molecular Medicine CIDR EPCR PfEMP1 severe childhood malaria var |
| title | Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains |
| title_full | Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains |
| title_fullStr | Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains |
| title_full_unstemmed | Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains |
| title_short | Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains |
| title_sort | plasmodium falciparum var genes expressed in children with severe malaria encode cidrα1 domains |
| topic | CIDR EPCR PfEMP1 severe childhood malaria var |
| url | https://doi.org/10.15252/emmm.201606188 |
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