Trends in Parasitology
SpotlightQuantitative sequencing confirms VSG diversity as central to immune evasion by Trypanosoma brucei
Section snippets
Acknowledgements
We thank J. David Barry for several discussions on this topic.
References (10)
Probabilistic order in antigenic variation of Trypanosoma brucei
Int. J. Parasitol.
(2005)Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens
Nat. Rev. Microbiol.
(2009)- et al.
Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure
Genome Res.
(2007) Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control
Cell. Microbiol.
(2013)DNA break site at fragile subtelomeres determines probability and mechanism of antigenic variation in African trypanosomes
PLoS Pathog.
(2013)
Cited by (18)
Emergence and adaptation of the cellular machinery directing antigenic variation in the African trypanosome
2022, Current Opinion in MicrobiologyCitation Excerpt :The contribution of VSG pseudogenes to the formation of novel ‘mosaic’ VSGs, which are distinct from any single (pseudo)gene in the silent archive, has long been known [33–35] (Figure 1b). The scale and complexity of the segmental gene-conversion reactions [36–40] that give rise to patchwork, functional mosaic VSGs have recently become clear. How — and indeed where in the genome — mosaic VSG recombination is catalysed is unknown; though a repair reaction termed microhomology-mediated end-joining (MMEJ) has been suggested to contribute [41], no test has been done.
Trypanosoma brucei ATR Links DNA Damage Signaling during Antigenic Variation with Regulation of RNA Polymerase I-Transcribed Surface Antigens
2020, Cell ReportsCitation Excerpt :Extensive evidence indicates that HR, catalyzed by RAD51 (McCulloch and Barry, 1999) and mediated by further factors (Hartley and McCulloch, 2008; Trenaman et al., 2013; Dobson et al., 2011; Proudfoot and McCulloch, 2005; Devlin et al., 2016; Kim and Cross, 2010, 2011), directs the switching of functionally intact VSGs. It is less clear how VSG pseudogenes are recombined, but the combinatorial assortment of these sequences generates huge levels of expressed VSG diversity in chronic infections (Marcello and Barry, 2007; Hall et al., 2013; Mugnier et al., 2015; McCulloch and Field, 2015; Jayaraman et al., 2019). As for transcriptional switching, the trigger for VSG recombination is still being sought, with BES DSBs (Boothroyd et al., 2009; Glover et al., 2013a), BES replication (Devlin et al., 2016, 2017; Benmerzouga et al., 2013), telomere shortening (Hovel-Miner et al., 2012), and RNA-DNA hybrids (Briggs et al., 2018; Nanavaty et al., 2017) having been suggested.
Innate immunomodulation to trypanosomatid parasite infections
2016, Experimental ParasitologyCitation Excerpt :The antigenic variation of VSGs is central to the virulence of African trypanosomes. The parasites have a large repertoire of antigenically distinct VSGs that are generated by mutation or recombination because the immune system is continually challenged by one new epitopes (McCulloch and Field, 2015). T. brucei VSGs play a central role in determining whether humans can be infected.
Combatting African Animal Trypanosomiasis (AAT) in livestock: The potential role of trypanotolerance
2016, Veterinary ParasitologyCitation Excerpt :Horn (2014), Manna et al. (2014) and Taylor and Rudenko (2006) have provided comprehensive reviews on the mechanisms of trypanosome antigenic variation. Although an increased understanding of the structure and mechanism of this antigenic variation of trypanosome parasites has occurred over the past 40 years, to date no vaccine is available (Manna et al., 2014; McCulloch and Field, 2015; Mony and Matthews, 2015). These factors are the main reasons why most research efforts aimed at developing a vaccine for trypanosomiasis have since shifted from variable surface (VSG) antigen towards the identification of other, invariant structural components of the parasite (Taylor, 1998; Alsford et al., 2013; Tsegaye et al., 2015).
All For One and One For All on the Tick-Host Battlefield
2016, Trends in ParasitologyCitation Excerpt :Another participant in the race to evade and/or exhaust the host immune system is antigenic variation, the simultaneous or sequential change in multiple antigens upon host immune system exposure. The mechanism of immune system exhaustion by continuous antigen switching is known to occur in Trypanosoma brucei, the causative agent of sleeping sickness, which can sequentially express around 2000 different surface antigens [46]. Every newly expressed antigen stimulates a massive immune reaction that eliminates the majority of parasites, but some of the surviving individuals with altered surface antigen expression escape from the host antigen-specific reaction and start a new round of multiplication.