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Background  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. 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.    Methods  Subfamilies 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.    Results  The 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.    Conclusions  The 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.

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