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

Autor:	Wichers JS; Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; Centre for Structural Systems Biology, Hamburg, Germany.; Biology Department, University of Hamburg, Hamburg, Germany., Tonkin-Hill G; Wellcome Sanger Institute, Hinxton, United Kingdom., Thye T; Epidemiology and Diagnostics, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany., Krumkamp R; Epidemiology and Diagnostics, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany., Kreuels B; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Germany, Hamburg, Germany.; Department of Medicine, College of Medicine, Blantyre, Malawi.; Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Strauss J; Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; Centre for Structural Systems Biology, Hamburg, Germany.; Biology Department, University of Hamburg, Hamburg, Germany., von Thien H; Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; Centre for Structural Systems Biology, Hamburg, Germany.; Biology Department, University of Hamburg, Hamburg, Germany., Scholz JA; Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany., Smedegaard Hansson H; CMP, University of Copenhagen, Copenhagen, Denmark., Weisel Jensen R; CMP, University of Copenhagen, Copenhagen, Denmark., Turner L; CMP, University of Copenhagen, Copenhagen, Denmark., Lorenz FR; Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany., Schöllhorn A; Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany., Bruchhaus I; Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; Biology Department, University of Hamburg, Hamburg, Germany., Tannich E; Epidemiology and Diagnostics, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany., Fendel R; Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Otto TD; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom., Lavstsen T; CMP, University of Copenhagen, Copenhagen, Denmark., Gilberger TW; Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; Centre for Structural Systems Biology, Hamburg, Germany.; Biology Department, University of Hamburg, Hamburg, Germany., Duffy MF; Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia., Bachmann A; Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; Centre for Structural Systems Biology, Hamburg, Germany.; Biology Department, University of Hamburg, Hamburg, Germany.; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Apr 28; Vol. 10. Date of Electronic Publication: 2021 Apr 28.
DOI:	10.7554/eLife.69040
Abstrakt:	Sequestration of Plasmodium falciparum ( P. falciparum )-infected erythrocytes to host endothelium through the parasite-derived P. falciparum erythrocyte membrane protein 1 ( 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 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, 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 naive immune status, and/or adverse inflammatory host responses to first infections favor the growth of EPCR-binding parasites. Competing Interests: JW, GT, TT, RK, BK, JS, Hv, JS, HS, RW, LT, FL, AS, IB, ET, RF, TO, TL, TG, MD, AB No competing interests declared (© 2021, Wichers et al.)
Databáze:	MEDLINE
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