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

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Common virulence gene expression in adult first-time infected malaria patients and severe cases. / Wichers, J Stephan; Tonkin-Hill, Gerry; Thye, Thorsten; Krumkamp, Ralf; Kreuels, Benno; Strauss, Jan; von Thien, Heidrun; Scholz, Judith Am; Smedegaard Hansson, Helle; Weisel Jensen, Rasmus; Turner, Louise; Lorenz, Freia-Raphaella; Schöllhorn, Anna; Bruchhaus, Iris; Tannich, Egbert; Fendel, Rolf; Otto, Thomas D; Lavstsen, Thomas; Gilberger, Tim W; Duffy, Michael F; Bachmann, Anna.

In: ELIFE, Vol. 10, e69040, 28.04.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wichers, JS, Tonkin-Hill, G, Thye, T, Krumkamp, R, Kreuels, B, Strauss, J, von Thien, H, Scholz, JA, Smedegaard Hansson, H, Weisel Jensen, R, Turner, L, Lorenz, F-R, Schöllhorn, A, Bruchhaus, I, Tannich, E, Fendel, R, Otto, TD, Lavstsen, T, Gilberger, TW, Duffy, MF & Bachmann, A 2021, 'Common virulence gene expression in adult first-time infected malaria patients and severe cases', ELIFE, vol. 10, e69040. https://doi.org/10.7554/eLife.69040

APA

Wichers, J. S., Tonkin-Hill, G., Thye, T., Krumkamp, R., Kreuels, B., Strauss, J., von Thien, H., Scholz, J. A., 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., ... Bachmann, A. (2021). Common virulence gene expression in adult first-time infected malaria patients and severe cases. ELIFE, 10, [e69040]. https://doi.org/10.7554/eLife.69040

Vancouver

Wichers JS, Tonkin-Hill G, Thye T, Krumkamp R, Kreuels B, Strauss J et al. Common virulence gene expression in adult first-time infected malaria patients and severe cases. ELIFE. 2021 Apr 28;10. e69040. https://doi.org/10.7554/eLife.69040

Bibtex

@article{dd6365dd93cc4782af16c174b7c692a7,
title = "Common virulence gene expression in adult first-time infected malaria patients and severe cases",
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.",
keywords = "Adult, CD36 Antigens/genetics, Cohort Studies, Endothelial Protein C Receptor/genetics, Female, Humans, Malaria, Falciparum/genetics, Male, Plasmodium falciparum/genetics, Protein Binding, Protozoan Proteins/genetics, Young Adult",
author = "Wichers, {J Stephan} and Gerry Tonkin-Hill and Thorsten Thye and Ralf Krumkamp and Benno Kreuels and Jan Strauss and {von Thien}, Heidrun and Scholz, {Judith Am} and {Smedegaard Hansson}, Helle and {Weisel Jensen}, Rasmus and Louise Turner and Freia-Raphaella Lorenz and Anna Sch{\"o}llhorn and Iris Bruchhaus and Egbert Tannich and Rolf Fendel and Otto, {Thomas D} and Thomas Lavstsen and Gilberger, {Tim W} and Duffy, {Michael F} and Anna Bachmann",
note = "{\textcopyright} 2021, Wichers et al.",
year = "2021",
month = apr,
day = "28",
doi = "10.7554/eLife.69040",
language = "English",
volume = "10",
journal = "ELIFE",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS

TY - JOUR

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

AU - Wichers, J Stephan

AU - Tonkin-Hill, Gerry

AU - Thye, Thorsten

AU - Krumkamp, Ralf

AU - Kreuels, Benno

AU - Strauss, Jan

AU - von Thien, Heidrun

AU - Scholz, Judith Am

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 - Otto, Thomas D

AU - Lavstsen, Thomas

AU - Gilberger, Tim W

AU - Duffy, Michael F

AU - Bachmann, Anna

N1 - © 2021, Wichers et al.

PY - 2021/4/28

Y1 - 2021/4/28

N2 - 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.

AB - 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.

KW - Adult

KW - CD36 Antigens/genetics

KW - Cohort Studies

KW - Endothelial Protein C Receptor/genetics

KW - Female

KW - Humans

KW - Malaria, Falciparum/genetics

KW - Male

KW - Plasmodium falciparum/genetics

KW - Protein Binding

KW - Protozoan Proteins/genetics

KW - Young Adult

U2 - 10.7554/eLife.69040

DO - 10.7554/eLife.69040

M3 - SCORING: Journal article

C2 - 33908865

VL - 10

JO - ELIFE

JF - ELIFE

SN - 2050-084X

M1 - e69040

ER -