Abstract
BackgroundAntigenic variation in Plasmodium falciparum involves switching among multicopy var gene family and is responsible for immune evasion and the maintenance of chronic infections. Current understanding of var gene expression and switching patterns comes from experiments conducted on long laboratory-adapted strains, with little known about their wild counterparts.MethodsGenome sequencing was used to obtain 50 var genes from a parasite isolated from the China-Myanmar border. Four clones with different dominant var genes were cultured in vitro in replicates for 50 generations. Transcription of the individual var gene was detected by real-time PCR and then the switching process was analysed.ResultsThe expression of multicopy var genes is mutually exclusive in clones of a wild P. falciparum isolate. The activation of distinct primary dominant var genes leads to different and favoured switching patterns in the four clones. The on/off rates of individual var genes are variable and the choice of subsequent dominant var genes are random, which results in the different switching patterns among replicates of each clonal wild P. falciparum isolate with near identical initial transcription profiles.ConclusionsThis study suggests that the switching patterns of var genes are abundant, which consist of both conserved and random parts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0565-y) contains supplementary material, which is available to authorized users.
Highlights
Antigenic variation in Plasmodium falciparum involves switching among multicopy var gene family and is responsible for immune evasion and the maintenance of chronic infections
Identification of 50 var genes in the genome of the wild Plasmodium falciparum isolate Four clones from the wild P. falciparum isolate FCYN0906 were obtained by limiting dilution, which exhibited identical genotypes when analysed with eight microsatellites
Studies on gene expression in the P. falciparum clone 3D7 have shown that the mutually exclusive expression of virulence genes is used by the parasite to slow the depletion of the limited number of genes contained in the multicopy var gene family [7,8]
Summary
Antigenic variation in Plasmodium falciparum involves switching among multicopy var gene family and is responsible for immune evasion and the maintenance of chronic infections. Switching among the expression of different var genes allows parasites to avoid the effects of the acquired immune response generated by the host against PfEMP1 and, to sustain a long-term infection. The effects of cellular memory ensure that most daughter parasites will express the same var gene [15,16,17]. This coordinates gene expression and ensures that the parasite’s repertoire of antigenic types is not rapidly exhausted
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