Molecular secrets of a parasite

Abstract

Research shows how the malaria parasite Plasmodium falciparum manipulates the expression of its var genes to avoid recognition by the host immune system. Four experts comment on the implications of these results for our understanding of gene regulation in general and the development of antimalaria vaccines. See Letter p.223 When the malaria parasite Plasmodium falciparum infects red blood cells, it escapes immune detection by expressing just one of 60 antigenically distinct var genes at a time, then switching to express a new gene during the course of infection. Here, Louis Miller and colleagues show that the histone H3 modification lysine 36 trimethylation (H3K36me3) is present at the transcription start site and along the gene body of silenced var genes. Knockout of the P. falciparum variant-silencing SET gene (PfSETvs) results in concurrent transcription of all 60 var genes, each one coding for a different version of the PfEMP1 membrane protein. PfSETvs therefore has a key role in var gene silencing. In addition, the PfSETvs knockout parasite generated in this work has potential as an antimalarial vaccine owing to its ability to express all PfEMP1 proteins, which should generate a broad repertoire of antibodies to protect against malaria.