Characterization and tissue-specific expression patterns of the Plasmodium chabaudi cir multigene family

Petra Ebbinghaus,Jürgen Krücken

doi:10.1186/1475-2875-10-272

Petra Ebbinghaus, Jürgen Krücken

Open Access

https://doi.org/10.1186/1475-2875-10-272

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Journal: Malaria journal	Publication Date: Sep 19, 2011
Citations: 66	License type: CC BY 2.0

Affiliation: Freie Universität Berlin

Abstract

BackgroundVariant antigens expressed on the surface of parasitized red blood cells (pRBCs) are important virulence factors of malaria parasites. Whereas Plasmodium falciparum erythrocyte membrane proteins 1 (PfEMP1) are responsible for sequestration of mature parasites, little is known about putative ligands mediating cytoadherence to host receptors in other Plasmodium species. Candidates include members of the pir superfamily found in the human parasite Plasmodium vivax (vir), in the simian pathogen Plasmodium knowlesi (kir) and in the rodent malarias Plasmodium yoelii (yir), Plasmodium berghei (bir) and Plasmodium chabaudi (cir). The aim of this study was to reveal a potential involvement of cir genes in P. chabaudi sequestration.MethodsSubfamilies of cir genes were identified by bioinformatic analyses of annotated sequence data in the Plasmodium Genome Database. In order to examine tissue-specific differences in the expression of cir mRNAs, RT-PCR with subfamily-specific primers was used. In total, 432 cDNA clones derived from six different tissues were sequenced to characterize the transcribed cir gene repertoire. To confirm differences in transcription profiles of cir genes, restriction fragment length polymorphism (RFLP) analyses were performed to compare different host tissues and to identify changes during the course of P. chabaudi infections in immunocompetent mice.ResultsThe phylogenetic analysis of annotated P. chabaudi putative CIR proteins identified two major subfamilies. Comparison of transcribed cir genes from six different tissues revealed significant differences in the frequency clones belonging to individual cir gene subgroups were obtained from different tissues. Further hints of difference in the transcription of cir genes in individual tissues were obtained by RFLP. Whereas only minimal changes in the transcription pattern of cir genes could be detected during the developmental cycle of the parasites, switching to expression of other cir genes during the course of an infection was observed around or after peak parasitemia.ConclusionsThe tissue-specific expression of cir mRNAs found in this study indicates correlation between expression of CIR antigens and distribution of parasites in inner organs. Together with comparable results for other members of the pir superfamily this suggests a role of cir and other pir genes in antigenic variation and sequestration of malaria parasites.

Highlights

Variant antigens expressed on the surface of parasitized red blood cells are important virulence factors of malaria parasites
In the most virulent human pathogen Plasmodium falciparum, the Plasmodium falciparum erythrocyte membrane proteins 1 (PfEMP1) protein family encoded by widely studied var genes was shown to be expressed at the surface of parasitized red blood cells (pRBCs) mediating the parasite binding to endothelial cells lining small blood vessels [9,10]
Phylogenetic analyses of putative CIR proteins in PlasmoDB A total of 199 putative CIR proteins had been annotated in the Plasmodium Genome Database Resource as cir genes

Summary

Introduction

Variant antigens expressed on the surface of parasitized red blood cells (pRBCs) are important virulence factors of malaria parasites. Whereas Plasmodium falciparum erythrocyte membrane proteins 1 (PfEMP1) are responsible for sequestration of mature parasites, little is known about putative ligands mediating cytoadherence to host receptors in other Plasmodium species. Malaria parasites have developed strategies to evade host immune responses by expressing a large and diverse repertoire of variant proteins on the surface of. In the most virulent human pathogen Plasmodium falciparum, the PfEMP1 protein family encoded by widely studied var genes was shown to be expressed at the surface of pRBC mediating the parasite binding to endothelial cells lining small blood vessels [9,10]. Further variant surface antigens encoded by multigene families were found in several other Plasmodium species infecting humans, monkeys and rodents [4,15,16,17]. Homologues of the var genes are not present in Plasmodium vivax or other malaria species [18], with exception of several var-like sequences from the chimpanzee parasite Plasmodium reichenowi [19], a close relative of P. falciparum

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