Evolution of Antigenic Variation in African Trypanosomes: Variant Surface Glycoprotein Expression, Structure, and Function

• Published in: BioEssays 2018-12, Vol.40 (12), p.e1800181-n/a
• Main Author: Bangs, James D.
• Format: Article
• Language: English
• Subjects: Ablation; Africa; African trypanosome; Antigenic Variation; Antigens; chronic diseases; Evolution; gene conversion; Gene Expression Regulation; Glycoproteins; Immune system; Infections; mammals; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - metabolism; parasites; protein folding; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; secretion; Structure-function relationships; Switching; Trypanosoma - genetics; Trypanosoma - immunology; Variant surface glycoprotein; variant surface glycoproteins
• ISSN: 0265-9247; 1521-1878; 1521-1878
• DOI: 10.1002/bies.201800181

The process of antigenic variation in parasitic African trypanosomes is a remarkable mechanism for outwitting the immune system of the mammalian host, but it requires a delicate balancing act for the monoallelic expression, folding and transport of a single variant surface glycoprotein (VSG). Only one of hundreds of VSG genes is expressed at time, and this from just one of ≈15 dedicated expression sites. By switching expression of VSGs the parasite presents a continuously shifting antigenic facade leading to prolonged chronic infections lasting months to years. The basics of VSG structure and switching have been known for several decades, but recent studies have brought higher resolution to many aspects this process. New VSG structures, in silico modeling of infections, studies of VSG codon usage, and experimental ablation of VSG expression provide insights that inform how this remarkable system may have evolved. African trypanosomes survive in the mammalian host by a finely tuned process of monoallelic antigenic variation. Only one of hundreds of variant surface glycoproteins is expressed at a time creating a dense surface coat covering the entire parasite. Many interrelated processes have contributed to the evolution of this remarkable system.