Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern
Public Library of Science
Copyright: © 2011 Recker et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection.
The work was funded by the Wellcome Trust (Grant No. 082130/Z/07/Z to CN) and the Rhodes Trust for support of AS. MR is funded by a Royal Society University Research Fellowship. SG is a Royal Society Wolfson Research Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
This is the final version of the article. Available from Public Library of Science via the DOI in this record.
Vol. 7 (3), article e1001306
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