Default Pathway of var2csa Switching and Translational Repression in Plasmodium falciparum
2008 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 3, no 4, e1982- p.Article in journal (Refereed) Published
Antigenic variation is a subtle process of fundamental importance to the survival of a microbial pathogen. In Plasmodium falciparum malaria, PfEMP1 is the major variable antigen and adhesin expressed at the surface of the infected erythrocyte, which is encoded for by members of a family of 60 var-genes. Peri-nuclear repositioning and epigenetic mechanisms control their mono-allelic expression. The switching of PfEMP1 depends in part on variable transition rates and short-lived immune responses to shared minor epitopes. Here we show var-genes to switch to a common gene that is highly transcribed, but sparsely translated into PfEMP1 and not expressed at the erythrocyte surface. Highly clonal and adhesive P. falciparum, which expressed distinct var-genes and the corresponding PfEMP1s at onset, were propagated without enrichment or panning. The parasites successively and spontaneously switched to transcribe a shared var-gene (var2csa) matched by the loss of PfEMP1 surface expression and host cell-binding. The var2csa gene repositioned in the peri-nuclear area upon activation, away from the telomeric clusters and heterochromatin to transcribe spliced, full-length RNA. Despite abundant transcripts, the level of intracellular PfEMP1 was low suggesting post-transcriptional mechanisms to partake in protein expression. In vivo, off-switching and translational repression may constitute one pathway, among others, coordinating PfEMP1 expression.
Place, publisher, year, edition, pages
2008. Vol. 3, no 4, e1982- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:kth:diva-47037DOI: 10.1371/journal.pone.0001982ISI: 000261558700007PubMedID: 18431472ScopusID: 2-s2.0-44349118501OAI: oai:DiVA.org:kth-47037DiVA: diva2:454668
QC 201111082011-11-082011-11-072011-11-08Bibliographically approved