Gene expression profiling of malaria parasites reveals common virulence gene expression in adult first-time infected patients and severe cases

Abstract

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 the same array of human endothelial receptor binding phenotypes. Here, we analyzed RNA-seq profiles of parasites isolated from 32 infected 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. Expression analysis of PfEMP1-encoding var genes showed that severe malaria was associated with expression of PfEMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-binding PfEMP1 was linked to non-severe malaria outcomes. In addition, gene expression-guided determination of parasite age, suggested that circulating parasites from non-severe malaria patients were older than parasites from severe malaria patients. First-time infected patients were also more likely to develop severe symptoms and tended to be infected for a longer period, which thus appeared to select for parasites with more sequestration-efficiency and therefore more pathogenic PfEMP1 variants.