Faria, J., Briggs, E. M., Black, J. A. and McCulloch, R. (2022) Emergence and adaptation of the cellular machinery directing antigenic variation in the African trypanosome. Current Opinion in Microbiology, 70, 102209. (doi: 10.1016/j.mib.2022.102209) (PMID:36215868)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Additional Information: | Work in RMcC’s lab is supported by a Wellcome Trust Investigator Award [224501/Z/21/Z] and by the Biotechnology and Biological Sciences Research Council (BBSRC) [BB/N016165/1, BB/R017166/1, BB/W001101/1]. EB is the recipient of a Wellcome Trust Sir Henry Wellcome Fellowship [218648/Z/19/Z], and JF is the recipient of a Wellcome Trust Sir Henry Dale Fellowship [222573/Z/21/Z]. JB is the recipient of a FAPESP Post-Doctoral Fellowship [2020/01883-7]. The Wellcome Centre for Integrative Parasitology is supported by core funding from the Wellcome Trust [104111]. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Black, Dr Jennifer Ann and Briggs, Miss Emma and McCulloch, Professor Richard |
| Creator Roles: | Briggs, E. M.Conceptualization, Writing – original draft, Writing – review and editing, Funding acquisition Black, J. A.Conceptualization, Writing – original draft, Writing – review and editing McCulloch, R.Conceptualization, Writing – original draft, Writing – review and editing, Funding acquisition |
| Authors: | Faria, J., Briggs, E. M., Black, J. A., and McCulloch, R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Current Opinion in Microbiology |
| Publisher: | Elsevier |
| ISSN: | 1369-5274 |
| ISSN (Online): | 1879-0364 |
| Published Online: | 07 October 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Current Opinion in Microbiology 2022 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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