Abstract
BackgroundThe pir genes comprise the largest multi-gene family in Plasmodium, with members found in P. vivax, P. knowlesi and the rodent malaria species. Despite comprising up to 5% of the genome, little is known about the functions of the proteins encoded by pir genes. P. chabaudi causes chronic infection in mice, which may be due to antigenic variation. In this model, pir genes are called cirs and may be involved in this mechanism, allowing evasion of host immune responses. In order to fully understand the role(s) of CIR proteins during P. chabaudi infection, a detailed characterization of the cir gene family was required.ResultsThe cir repertoire was annotated and a detailed bioinformatic characterization of the encoded CIR proteins was performed. Two major sub-families were identified, which have been named A and B. Members of each sub-family displayed different amino acid motifs, and were thus predicted to have undergone functional divergence. In addition, the expression of the entire cir repertoire was analyzed via RNA sequencing and microarray. Up to 40% of the cir gene repertoire was expressed in the parasite population during infection, and dominant cir transcripts could be identified. In addition, some differences were observed in the pattern of expression between the cir subgroups at the peak of P. chabaudi infection. Finally, specific cir genes were expressed at different time points during asexual blood stages.ConclusionsIn conclusion, the large number of cir genes and their expression throughout the intraerythrocytic cycle of development indicates that CIR proteins are likely to be important for parasite survival. In particular, the detection of dominant cir transcripts at the peak of P. chabaudi infection supports the idea that CIR proteins are expressed, and could perform important functions in the biology of this parasite. Further application of the methodologies described here may allow the elucidation of CIR sub-family A and B protein functions, including their contribution to antigenic variation and immune evasion.
Highlights
The pir genes comprise the largest multi-gene family in Plasmodium, with members found in P. vivax, P. knowlesi and the rodent malaria species
Up to 40% of the cir gene repertoire was expressed in the parasite population during infection, and dominant cir transcripts could be identified, with some differences in the pattern of expression between the cir subgroups
The majority of cir genes contained one predicted TM domain including some of the divergent cirs. b) Sequence similarity of CIR proteins In order to investigate similarity between CIRs, the amino acid sequences identified during cir gene annotation were aligned using Muscle [39], and refined manually (Additional file 1a)
Summary
The pir genes comprise the largest multi-gene family in Plasmodium, with members found in P. vivax, P. knowlesi and the rodent malaria species. Surface proteins or variant surface antigens (VSA) have been identified so far in three species infecting humans: Plasmodium falciparum, P. vivax and P. knowlesi, as well as in the rodent malaria parasites P. chabaudi and P. yoelii [1,2,3,4,5]. These proteins are implicated in antigenic variation and immune evasion, as well. Atype RIFINs may be more likely to play a role in the host/parasite relationship during the blood stages of P. falciparum
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