PfEMP1-DBL1alpha Amino Acid Motifs in Severe Disease States of Plasmodium Falciparum Malaria

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Sep 27

PMID 17895392

Citations 55

Authors

Johan Normark

Daniel Nilsson

Ulf Ribacke

Gerhard Winter

Kirsten Moll

Craig E Wheelock

Justus Bayarugaba

Fred Kironde

Thomas G Egwang

Qijun Chen

Bjorn Andersson

Mats Wahlgren

Affiliations

Soon will be listed here.

Abstract

An infection with Plasmodium falciparum may lead to severe malaria as a result of excessive binding of infected erythrocytes in the microvasculature. Vascular adhesion is mediated by P. falciparum erythrocyte membrane protein-1 (PfEMP1), which is encoded for by highly polymorphic members of the var-gene family. Here, we profile var gene transcription in fresh P. falciparum trophozoites from Ugandan children with malaria through var-specific DBL1alpha-PCR amplification and sequencing. A method for subsectioning region alignments into homology areas (MOTIFF) was developed to examine collected sequences. Specific PfEMP1-DBL1alpha amino acid motifs correlated with rosetting and severe malaria, with motif location corresponding to distinct regions of receptor interaction. The method is potentially applicable to other families of variant proteins and may be useful in identifying sequence-phenotype relationships. The results suggest that certain PfEMP1 sequences are predisposed to inducing severe malaria.

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