Common virulence gene expression in adult first-time infected malaria patients and severe cases
Year: 2021
Type: article
Study design: Observational Study
Abstract: Sequestration of Plasmodium falciparum -infected erythrocytes to host endothelium through the parasite-derived Pf EMP1 adhesion proteins is central to the development of malaria pathogenesis. Pf EMP1 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 travelers returning to Germany. Patients were categorized into either malaria naïve (n=15) or pre-exposed (n=17), and into severe (n=8) or non-severe (n=24) cases. For differential expression analysis of Pf EMP1-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 Pf EMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-binding Pf EMP1 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 Pf EMP1 variants are more common in patients with a naïve immune status and/or adverse inflammatory host responses to first infections favors growth of EPCR-binding parasites.
Source: eLife
DOI: 10.7554/elife.69040
Authors: Jan Stephan Wichers, Gerry Tonkin-Hill, Thorsten Thye, Ralf Krumkamp, Benno Kreuels, Jan Strauss, Heidrun von Thien, Judith Anna Marie Scholz, Helle Smedegaard Hansson, Rasmus Weisel Jensen, Louise Turner, Freia-Raphaella Lorenz, Anna Schöllhorn, Iris Bruchhaus, Egbert Tannich, Rolf Fendel, Thomas Dan Otto, Thomas Lavstsen, Tim-Wolf Gilberger, Michael Frank Duffy, Anna Bachmann
Institutions: Universität Hamburg, Centre for Structural Systems Biology, Bernhard Nocht Institute for Tropical Medicine, Wellcome Sanger Institute, German Center for Infection Research, University Medical Center Hamburg-Eppendorf, University of Copenhagen, University of Tübingen, University of Glasgow, The University of Melbourne
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Deutsches Zentrum für Infektionsforschung, Wellcome Trust, Deutsche Forschungsgemeinschaft, Lundbeckfonden, Danmarks Frie Forskningsfond, Universität Hamburg, Kirsten og Freddy Johansens Fond, H. Lundbeck A/S, Medical Research Council, National Health and Medical Research Council, Deutsches Elektronen-Synchrotron
OpenAlex ID: W3159706041