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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

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

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  • Media type: E-Article
  • Title: Common virulence gene expression in adult first-time infected malaria patients and severe cases
  • Contributor: 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
  • imprint: eLife Sciences Publications, Ltd, 2021
  • Published in: eLife
  • Language: English
  • DOI: 10.7554/elife.69040
  • ISSN: 2050-084X
  • Origination:
  • Footnote:
  • Description: <jats:p>Sequestration of <jats:italic>Plasmodium falciparum</jats:italic>(<jats:italic>P. falciparum</jats:italic>)-infected erythrocytes to host endothelium through the parasite-derived <jats:italic>P. falciparum</jats:italic> erythrocyte membrane protein 1 (<jats:italic>Pf</jats:italic>EMP1) adhesion proteins is central to the development of malaria pathogenesis. <jats:italic>Pf</jats:italic>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 <jats:italic>P. falciparum-</jats:italic>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, <jats:italic>Pf</jats:italic>EMP1-encoding <jats:italic>var</jats:italic> gene transcripts were de novo assembled from RNA-seq data and, in parallel, <jats:italic>var-</jats:italic>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 <jats:italic>Pf</jats:italic>EMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-binding <jats:italic>Pf</jats:italic>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 <jats:italic>Pf</jats:italic>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.</jats:p>
  • Access State: Open Access