Abstract

BackgroundPlasmodium interspersed repeat (pir) is the largest multigene family in the genomes of most Plasmodium species. A variety of functions for the PIR proteins which they encode have been proposed, including antigenic variation, immune evasion, sequestration and rosetting. However, direct evidence for these is lacking. The repetitive nature of the family has made it difficult to determine function experimentally. However, there has been some success in using gene expression studies to suggest roles for some members in virulence and chronic infection.MethodsHere pir gene expression was examined across the life cycle of Plasmodium berghei using publicly available RNAseq data-sets, and at high resolution in the intraerythrocytic development cycle using new data from Plasmodium chabaudi.ResultsExpression of pir genes is greatest in stages of the parasite which invade and reside in red blood cells. The marked exception is that liver merozoites and male gametocytes produce a very large number of pir gene transcripts, notably compared to female gametocytes, which produce relatively few. Within the asexual blood stages different subfamilies peak at different times, suggesting further functional distinctions. Representing a subfamily of its own, the highly conserved ancestral pir gene warrants further investigation due to its potential tractability for functional investigation. It is highly transcribed in multiple life cycle stages and across most studied Plasmodium species and thus is likely to play an important role in parasite biology.ConclusionsThe identification of distinct expression patterns for different pir genes and subfamilies is likely to provide a basis for the design of future experiments to uncover their function.

Highlights

  • Plasmodium interspersed repeat is the largest multigene family in the genomes of most Plasmodium species

  • It has been suggested that the pir family fulfils similar roles in immune evasion and pathogenesis as P. falciparum var, there is no direct evidence for this, and the function(s) of pirs remains largely unknown

  • Some proteomic and immunofluorescence studies show PIR proteins on the surface of infected RBCs, other studies indicate that they are present in the host or parasite cytoplasm, or on the parasitophorous vacuole [6, 16,17,18,19] suggesting multiple different functions for PIR proteins during blood-stage infections

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Summary

Introduction

Plasmodium interspersed repeat (pir) is the largest multigene family in the genomes of most Plasmodium species. The genomes of the malaria parasites (Plasmodium spp.) contain a variety of multigene families These are generally located in the sub-telomeric regions of chromosomes, a feature which is thought to allow regulation of gene expression by heterochromatin and promote diversification of the gene sequences through recombination [1,2,3]. It has been suggested that the pir family fulfils similar roles in immune evasion and pathogenesis as P. falciparum var, there is no direct evidence for this, and the function(s) of pirs remains largely unknown. Chabaudi (AS strain) infections of mice, different pir subfamilies are associated with the acute and chronic phases of the infection, and parasites from the two phases of infection are differently virulent [20] This association suggests pir gene expression may affect virulence of blood-stage P. chabaudi, and that pir genes could be involved in evading the initial immune response. These data represent only the most highly expressed genes, they suggest there may be different functions for pir genes between asexual and sexual blood stages

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