Abstract
Virulence of the most deadly malaria parasite Plasmodium falciparum is linked to the variant surface antigen PfEMP1, which is encoded by about 60 var genes per parasite genome. Although the expression of particular variants has been associated with different clinical outcomes, little is known about var gene expression at the onset of infection. By analyzing controlled human malaria infections via quantitative real-time PCR, we show that parasite populations from 18 volunteers expressed virtually identical transcript patterns that were dominated by the subtelomeric var gene group B and, to a lesser extent, group A. Furthermore, major changes in composition and frequency of var gene transcripts were detected between the parental parasite culture that was used to infect mosquitoes and Plasmodia recovered from infected volunteers, suggesting that P. falciparum resets its var gene expression during mosquito passage and starts with the broad expression of a specific subset of var genes when entering the human blood phase.
Highlights
Malaria is one of the most frequently occurring parasitic diseases worldwide with an estimated 198 million clinical cases in 2013 and a death toll of more than 0.5 million [1]
A repertoire of 60 var genes codes for a broad range of different variant antigens presented on the surface of infected erythrocytes
To better understand antigenic variation in vivo we analyzed the var gene expression profiles in blood samples from 18 malaria naïve volunteers, who were experimentally infected with cryopreserved sporozoites isolated from Anopheles mosquitoes
Summary
Malaria is one of the most frequently occurring parasitic diseases worldwide with an estimated 198 million clinical cases in 2013 and a death toll of more than 0.5 million [1]. Each parasite possesses about 60 var genes coding for different PfEMP1 variants, which are expressed in a mutually exclusive manner meaning that generally only a single PfEMP1 variant is exposed on the surface of the infected erythrocyte at a time while all other gene copies are silenced [6]. The global var gene repertoire present in the parasite population was assumed to be highly diverse and the number of variants almost unlimited. The comparison of seven P. falciparum genomes revealed 23 PfEMP1 domain cassettes (DCs), which seem to form conserved recombination and receptor-binding units [10]. Both observations point to a more conserved var gene repertoire than previously assumed
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