Molecular mechanisms underlying the control of antigenic variation in African trypanosomes.
Bottom Line: The 'pre-genomic' era saw the identification of the range of pathways involving VSG recombination in the context of mono-telomeric VSG transcription.A prominent feature of the early post-genomic era is the description of the molecular machineries involved in these processes.We describe the factors and sequences recently linked to mutually exclusive transcription and VSG recombination, and how these act in the control of the key virulence mechanism of antigenic variation.
Affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. email@example.comShow MeSH
Mentions: Many pathogens have evolved strategies for phenotypic and clonal variation of surface proteins. This allows for the establishment of a persistent infection in immunocompetent hosts, enhancing transmission. The African trypanosome, Trypanosoma brucei, is one such pathogen; a protozoan of major medical and economic importance. These highly motile cells circulate in the mammalian host bloodstream and are spread by tsetse flies. Evasion of the adaptive host immune response is achieved by changing the composition of a dense Variant Surface Glycoprotein (VSG) coat on bloodstream form cells . The VSG is invariably encoded in a polycistronically transcribed telomeric expression site (ES). Importantly, VSG expression is monoallelic such that only one among 10–20 telomeric ESs is transcribed at a time . Silencing at all other ESs maintains monoallelic expression and the integrity of the evasion strategy while the multiplicity of potential ESs (Figure 1) allows for a co-ordinated switch to transfer active transcription from one telomere to another . Beyond the VSGs found in the ES, T. brucei also possesses a massive archive of ∼1000 silent VSGs and VSG pseudogenes which dominate subtelomeres . Recombination is therefore central to antigenic variation, allowing the parasite to utilise this VSG archive, typically by copying a different gene into the active ES (Figure 1).
Affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. firstname.lastname@example.org