Mosquito Passage Dramatically Changes var Gene Expression in Controlled Human Plasmodium falciparum Infections

PLoS Pathog. 2016 Apr 12;12(4):e1005538. doi: 10.1371/journal.ppat.1005538. eCollection 2016 Apr.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigenic Variation / genetics*
  • Antigenic Variation / immunology
  • Culicidae
  • Gene Expression / genetics*
  • Humans
  • Malaria, Falciparum / parasitology*
  • Malaria, Falciparum / transmission
  • Plasmodium falciparum / genetics*
  • Protozoan Proteins / genetics
  • RNA, Messenger / genetics

Substances

  • Protozoan Proteins
  • RNA, Messenger

Grant support

The clinical trial and the var gene expression analysis were supported by the Federal Ministry of Education and Research in the framework of the German Centre for Infection Research (DZIF) (WP4). RK, BM and PGK received funding by the German Center for Infection Research (DZIF) (WP4). The publication of this article was funded by the Open Access Fund of the Leibniz Association. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.