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

Autor: Daniel T. R. Minja, Louise Turner, Thor G. Theander, Sixbert I. Mkumbaye, Jens E.V. Petersen, Thomas Lavstsen, John Lusingu, Jakob S. Jespersen, Bent O. Petersen, Christian W. Wang
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
030231 tropical medicine
Protein domain
Plasmodium falciparum
Protozoan Proteins
Receptors
Cell Surface
macromolecular substances
Biology
CIDR
Chromatin
Epigenetics
Genomics & Functional Genomics
Pathogenesis
Transcriptome
03 medical and health sciences
EPCR
0302 clinical medicine
SDG 3 - Good Health and Well-being
Protein Domains
Antigens
CD
Report
parasitic diseases
Humans
Malaria
Falciparum
var
Gene
Endothelial protein C receptor
severe childhood malaria
Gene Expression Profiling
Endothelial Protein C Receptor
Infant
biology.organism_classification
Virology
Microbiology
Virology & Host Pathogen Interaction
Severe childhood malaria
PfEMP1
030104 developmental biology
Cerebral Malaria
Child
Preschool
Immunology
Adjunctive treatment
Host-Pathogen Interactions
Molecular Medicine
Female
Protein Binding
Reports
Zdroj: EMBO Molecular Medicine
Jespersen, J S, Wang, C W, Mkumbaye, S I, Minja, D T, Petersen, B, Turner, L, Petersen, J E, Lusingu, J P, Theander, T G & Lavstsen, T 2016, ' Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains ', EMBO Molecular Medicine, vol. 8, no. 8, pp. 839-850 . https://doi.org/10.15252/emmm.201606188
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, vol. 8, no. 7, pp. 685-829 . https://doi.org/10.15252/emmm.201606188
ISSN: 1757-4684
DOI: 10.15252/emmm.201606188
Popis: 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.
Databáze: OpenAIRE
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