TY - JOUR

T1 - Common virulence gene expression in adult first-time infected malaria patients and severe cases

AU - Wichers, Jan Stephan

AU - Tonkin-Hill, Gerry

AU - Thye, Thorsten

AU - Krumkamp, Ralf

AU - Kreuels, Benno

AU - Strauss, Jan

AU - von Thien, Heidrun

AU - Scholz, Judith Anna Marie

AU - Smedegaard Hansson, Helle

AU - Weisel Jensen, Rasmus

AU - Turner, Louise

AU - Lorenz, Freia-Raphaella

AU - Schöllhorn, Anna

AU - Bruchhaus, Iris

AU - Tannich, Egbert

AU - Fendel, Rolf

AU - D Otto, Thomas

AU - Lavstsen, Thomas

AU - Gilberger, Tim Wolf

AU - Duffy, Michael

AU - Bachmann, Anna

N1 - © 2021, Wichers et al.

PY - 2021

Y1 - 2021

N2 - Sequestration of Plasmodium falciparum-infected erythrocytes to host endothelium through the parasite-derived 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 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 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 naïve immune status and/or adverse inflammatory host responses to first infections favors growth of EPCR-binding parasites.

AB - Sequestration of Plasmodium falciparum-infected erythrocytes to host endothelium through the parasite-derived 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 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 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 naïve immune status and/or adverse inflammatory host responses to first infections favors growth of EPCR-binding parasites.

U2 - 10.7554/eLife.69040

DO - 10.7554/eLife.69040

M3 - Journal article

C2 - 33908865

VL - 10

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e69040

ER -