Evolution of the variant surface glycoprotein family in African trypanosomes

• Published in: Trends in parasitology Vol. 38; no. 1; pp. 23 - 36
• Main Authors: Silva Pereira, Sara, Jackson, Andrew P., Figueiredo, Luísa M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2022
• Subjects: African trypanosomes; African trypanosomiasis; Animals; antigenic diversity; antigenic variation; Antigenic Variation - genetics; Membrane Glycoproteins - genetics; nagana; Trypanosoma; Trypanosoma brucei brucei - genetics; Trypanosomiasis, African - parasitology; variant surface glycoproteins; Variant Surface Glycoproteins, Trypanosoma - genetics; Variant Surface Glycoproteins, Trypanosoma - metabolism; African trypanosomes; antigenic variation; nagana; variant surface glycoproteins; antigenic diversity; African trypanosomiasis
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2021.07.012

An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family and fundamental to both immune evasion and disease epidemiology within host populations. Recent studies have revealed that the VSG repertoire has a complex evolutionary history. Sequence diversity, genomic organization, and expression patterns are species-specific, which may explain other variations in parasite virulence and disease pathology. Evidence also shows that we may be underestimating the extent to what VSGs are repurposed beyond their roles as variant antigens, establishing a need to examine VSG functionality more deeply. Here, we review sequence variation within the VSG gene family, and highlight the many opportunities to explore their likely diverse contributions to parasite survival. Research into variant antigen diversity has grown in recent years due to advances in sequencing and computational methods. We now have tools to assess the diversity and expression of variant surface glycoproteins (VSGs) systematically, and in depth, in multiple Trypanosoma species and in many strains.Despite a common phenotype of antigenic variation, African trypanosome species have adopted distinct approaches to the generation of antigenic novelty, which affects the mechanism of antigenic variation per se and infection-persistence strategies.Evidence for functional differentiation amongst the VSG repertoire points towards VSGs playing important roles in the host–trypanosome interaction beyond antigenic variation. Future research will dissect alternative functions of VSGs.