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Lookup NU author(s): Dr Emma BriggsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Survival of the African trypanosome within its mammalian hosts, and hence transmission between hosts, relies upon antigenic variation, where stochastic changes in the composition of their protective variant-surface glycoprotein (VSG) coat thwart effective removal of the pathogen by adaptive immunity. Antigenic variation has evolved remarkable mechanistic complexity in Trypanosoma brucei, with switching of the VSG coat executed by either transcriptional or recombination reactions. In the former, a single T. brucei cell selectively transcribes one telomeric VSG transcription site, termed the expression site (ES), from a pool of around 15. Silencing of the active ES and activation of one previously silent ES can lead to a co-ordinated VSG coat switch. Outside the ESs, the T. brucei genome contains an enormous archive of silent VSG genes and pseudogenes, which can be recombined into the ES to execute a coat switch. Most such recombination involves gene conversion, including copying of a complete VSG and more complex reactions where novel 'mosaic' VSGs are formed as patchworks of sequences from several silent (pseudo)genes. Understanding of the cellular machinery that directs transcriptional and recombination VSG switching is growing rapidly and the emerging picture is of the use of proteins, complexes and pathways that are not limited to trypanosomes, but are shared across the wider grouping of kinetoplastids and beyond, suggesting co-option of widely used, core cellular reactions. We will review what is known about the machinery of antigenic variation and discuss if there remains the possibility of trypanosome adaptations, or even trypanosome-specific machineries, that might offer opportunities to impair this crucial parasite-survival process.
Author(s): Faria J, Briggs EM, Black JA, McCulloch R
Publication type: Article
Publication status: Published
Journal: Current Opinion in Microbiology
Year: 2022
Volume: 70
Print publication date: 01/12/2022
Online publication date: 07/10/2022
Acceptance date: 04/09/2022
Date deposited: 26/02/2025
ISSN (print): 1369-5274
ISSN (electronic): 1879-0364
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.mib.2022.102209
DOI: 10.1016/j.mib.2022.102209
PubMed id: 36215868
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