Expression of the Domain Cassette 8 Plasmodium Falciparum Erythrocyte Membrane Protein 1 Is Associated With Cerebral Malaria in Benin

PLoS One. 2013 Jul 29;8(7):e68368. doi: 10.1371/journal.pone.0068368. Print 2013.

Abstract

Background: Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a highly polymorphic adherence receptor expressed on the surface of infected erythrocytes. Based on sequence homology PfEMP-1 variants have been grouped into three major groups A-C, the highly conserved VAR2CSA variants, and semi-conserved types defined by tandem runs of specific domains ("domain cassettes" (DC)). The PfEMP-1 type expressed determines the adherence phenotype, and is associated with clinical outcome of infection.

Methods: Parasite isolates from Beninese children or women presenting with, respectively, CM or PAM were collected along with samples from patients with uncomplicated malaria (UM). We assessed the transcript level of var genes by RT-qPCR and the expression of PfEMP-1 proteins by LC-MS/MS.

Results: Var genes encoding DC8 and Group A PfEMP-1 were transcribed more often and at higher levels in cerebral malaria vs. uncomplicated malaria patients. LC-MS/MS identified peptides from group A, DC8 PfEMP-1 more frequently in cerebral malaria than in uncomplicated malaria and pregnancy-associated malaria samples.

Conclusion: This is the first study to show association between PfEMP-1 subtype and disease outcome by direct analysis of parasites proteome. The results corroborate that group A and specifically the PfEMP-1 types DC8 are universally associated with cerebral malaria. This is a crucial observation for promoting studies on malaria pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Benin
  • Child
  • Child, Preschool
  • Chromatography, Liquid
  • Female
  • Gene Expression Regulation
  • Genes, Protozoan
  • Humans
  • Malaria, Cerebral / genetics
  • Malaria, Cerebral / parasitology*
  • Mass Spectrometry
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / physiology*
  • Pregnancy
  • Pregnancy Complications, Parasitic / genetics
  • Pregnancy Complications, Parasitic / parasitology
  • Protein Structure, Tertiary
  • Proteomics
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Protozoan Proteins
  • RNA, Messenger
  • erythrocyte membrane protein 1, Plasmodium falciparum

Grant support

The work was supported by IRD and Gr-Ex. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.