Common virulence gene expression in adult first-time infected malaria patients and severe cases

Wichers, J. S. et al. (2021) Common virulence gene expression in adult first-time infected malaria patients and severe cases. eLife, 10, e69040. (doi: 10.7554/elife.69040) (PMID:33908865) (PMCID:PMC8102065)

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Abstract

Sequestration of Plasmodium falciparum(P. falciparum)-infected erythrocytes to host endothelium through the parasite-derived P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins is central to the development of malaria pathogenesis. PfEMP1 proteins have diversified and expanded to encompass many sequence variants, conferring each parasite a similar array of human endothelial receptor-binding phenotypes. Here, we analyzed RNA-seq profiles of parasites isolated from 32 P. falciparum-infected adult travellers returning to Germany. Patients were categorized into either malaria naive (n = 15) or pre-exposed (n = 17), and into severe (n = 8) or non-severe (n = 24) cases. For differential expression analysis, PfEMP1-encoding var gene transcripts were de novo assembled from RNA-seq data and, in parallel, var-expressed sequence tags were analyzed and used to predict the encoded domain composition of the transcripts. Both approaches showed in concordance that severe malaria was associated with PfEMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-binding PfEMP1 was linked to non-severe malaria outcomes. First-time infected adults were more likely to develop severe symptoms and tended to be infected for a longer period. Thus, parasites with more pathogenic PfEMP1 variants are more common in patients with a naive immune status, and/or adverse inflammatory host responses to first infections favor the growth of EPCR-binding parasites.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Otto, Dr Thomas
Creator Roles:
Otto, T. D.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – review and editing
Authors: Wichers, J. S., Tonkin-Hill, G., Thye, T., Krumkamp, R., Kreuels, B., Strauss, J., von Thien, H., Scholz, J. A.M., Smedegaard Hansson, H., Weisel Jensen, R., Turner, L., Lorenz, F.-R., Schöllhorn, A., Bruchhaus, I., Tannich, E., Fendel, R., Otto, T. D., Lavstsen, T., Gilberger, T. W., Duffy, M. F., and Bachmann, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications, Ltd
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2021 Wichers et al.
First Published:First published in eLife 10:e69040
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZRIII - Parasitology