Antigenic variation in Plasmodium falciparum: moving beyond the laboratory strains

Antigenic variation in Plasmodium falciparum malaria is mediated by the multicopy var gene gene family. Each parasite carries approximately 60 different var genes. A system of mutually exclusive expression ensures that only one gene is expressed in each individual cell. This ensures that only 1 of the 60 variants is exposed to the immune system. Switches in var gene expression result in antigenic variation. During recent years there has been a remarkable progress in the understanding of the mechanisms that regulate var gene expression. Genetic elements such as the var gene intron, chromatin modifications and nuclear repositioning have all been implicated in the control of this large and diverse gene family. It has also been shown that var gene expression in clonal cultures is relatively stable over long periods of time, suggesting that an imprinted epigenetic program coordinates the expression of the gene family. Most of the recent advances in var gene biology have been generated through experiments with laboratory adapted parasite lines. This raises 2 central questions: 1. Does var gene expression in laboratory isolates resemble var gene expression in field isolates? 2. How does the immune system influence var gene expression in natural infections? To start to address these questions, we embarked on a series of experiments studying var gene expression in parasites recently obtained from asymptomatically infected adults from Lambaréné, Gabon.