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

Overview

Journal Bioessays

Publisher Wiley

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Oct 30

PMID 30370931

Citations 23

Authors

James D Bangs

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Multifunctional roles of Sec13 paralogues in the euglenozoan .

Sharif M, Greenberg L, Bangs J Open Biol. 2025; 15(2):240324.

PMID: 39999875 PMC: 11858755. DOI: 10.1098/rsob.240324.

Multifunctional Roles of Sec13 Paralogues in the Euglenozoan .

Sharif M, Greenberg L, Bangs J bioRxiv. 2024; .

PMID: 39677643 PMC: 11642865. DOI: 10.1101/2024.12.03.626618.

Meta-analysis of the Vmp-like sequences of Lyme disease : evidence for the evolution of an elaborate antigenic variation system.

Norris S, Brangulis K Front Microbiol. 2024; 15:1469411.

PMID: 39450289 PMC: 11499132. DOI: 10.3389/fmicb.2024.1469411.

Beyond the VSG layer: Exploring the role of intrinsic disorder in the invariant surface glycoproteins of African trypanosomes.

Sulzen H, Volkov A, Geens R, Zahedifard F, Stijlemans B, Zoltner M PLoS Pathog. 2024; 20(4):e1012186.

PMID: 38648216 PMC: 11065263. DOI: 10.1371/journal.ppat.1012186.

Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2.

Rogozin I, Saura A, Poliakov E, Bykova A, Roche-Lima A, Pavlov Y Int J Mol Sci. 2024; 25(7).

PMID: 38612505 PMC: 11011937. DOI: 10.3390/ijms25073696.

References

Horn D . Codon usage suggests that translational selection has a major impact on protein expression in trypanosomatids. BMC Genomics. 2008; 9:2. PMC: 2217535. DOI: 10.1186/1471-2164-9-2. View

Pinger J, Nesic D, Ali L, Aresta-Branco F, Lilic M, Chowdhury S . African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat. Nat Microbiol. 2018; 3(8):932-938. PMC: 6108419. DOI: 10.1038/s41564-018-0187-6. View

Seyfang A, Mecke D, Duszenko M . Degradation, recycling, and shedding of Trypanosoma brucei variant surface glycoprotein. J Protozool. 1990; 37(6):546-52. DOI: 10.1111/j.1550-7408.1990.tb01263.x. View

Carrington M, Miller N, Blum M, Roditi I, Wiley D, Turner M . Variant specific glycoprotein of Trypanosoma brucei consists of two domains each having an independently conserved pattern of cysteine residues. J Mol Biol. 1991; 221(3):823-35. DOI: 10.1016/0022-2836(91)80178-w. View

Bangs J, Andrews N, Hart G, Englund P . Posttranslational modification and intracellular transport of a trypanosome variant surface glycoprotein. J Cell Biol. 1986; 103(1):255-63. PMC: 2113794. DOI: 10.1083/jcb.103.1.255. View

Tiengwe C, Koeller C, Bangs J . Endoplasmic reticulum-associated degradation and disposal of misfolded GPI-anchored proteins in Trypanosoma brucei. Mol Biol Cell. 2018; 29(20):2397-2409. PMC: 6233060. DOI: 10.1091/mbc.E18-06-0380. View

Zimmermann H, Subota I, Batram C, Kramer S, Janzen C, Jones N . A quorum sensing-independent path to stumpy development in Trypanosoma brucei. PLoS Pathog. 2017; 13(4):e1006324. PMC: 5398725. DOI: 10.1371/journal.ppat.1006324. View

Berberof M, Vanhamme L, Tebabi P, Pays A, Jefferies D, Welburn S . The 3'-terminal region of the mRNAs for VSG and procyclin can confer stage specificity to gene expression in Trypanosoma brucei. EMBO J. 1995; 14(12):2925-34. PMC: 398412. DOI: 10.1002/j.1460-2075.1995.tb07292.x. View

Duszenko M, Ivanov I, Ferguson M, Plesken H, Cross G . Intracellular transport of a variant surface glycoprotein in Trypanosoma brucei. J Cell Biol. 1988; 106(1):77-86. PMC: 2114957. DOI: 10.1083/jcb.106.1.77. View

10.

Hertz-Fowler C, Figueiredo L, Quail M, Becker M, Jackson A, Bason N . Telomeric expression sites are highly conserved in Trypanosoma brucei. PLoS One. 2008; 3(10):e3527. PMC: 2567434. DOI: 10.1371/journal.pone.0003527. View

11.

Gunzl A, Bruderer T, Laufer G, Schimanski B, Tu L, Chung H . RNA polymerase I transcribes procyclin genes and variant surface glycoprotein gene expression sites in Trypanosoma brucei. Eukaryot Cell. 2003; 2(3):542-51. PMC: 161450. DOI: 10.1128/EC.2.3.542-551.2003. View

12.

Freymann D, Down J, Carrington M, Roditi I, Turner M, Wiley D . 2.9 A resolution structure of the N-terminal domain of a variant surface glycoprotein from Trypanosoma brucei. J Mol Biol. 1990; 216(1):141-60. DOI: 10.1016/S0022-2836(05)80066-X. View

13.

Navarro M, Gull K . A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei. Nature. 2001; 414(6865):759-63. DOI: 10.1038/414759a. View

14.

Bangs J . Replication of the ERES:Golgi junction in bloodstream-form African trypanosomes. Mol Microbiol. 2011; 82(6):1433-43. PMC: 3237776. DOI: 10.1111/j.1365-2958.2011.07900.x. View

15.

Hall J, Wang H, Barry J . Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation. PLoS Pathog. 2013; 9(7):e1003502. PMC: 3708902. DOI: 10.1371/journal.ppat.1003502. View

16.

Tiengwe C, Bush P, Bangs J . Controlling transferrin receptor trafficking with GPI-valence in bloodstream stage African trypanosomes. PLoS Pathog. 2017; 13(5):e1006366. PMC: 5426795. DOI: 10.1371/journal.ppat.1006366. View

17.

Clayton C . Gene expression in Kinetoplastids. Curr Opin Microbiol. 2016; 32:46-51. DOI: 10.1016/j.mib.2016.04.018. View

18.

Trindade S, Rijo-Ferreira F, Carvalho T, Pinto-Neves D, Guegan F, Aresta-Branco F . Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice. Cell Host Microbe. 2016; 19(6):837-48. PMC: 4906371. DOI: 10.1016/j.chom.2016.05.002. View

19.

Ridewood S, Ooi C, Hall B, Trenaman A, Wand N, Sioutas G . The role of genomic location and flanking 3'UTR in the generation of functional levels of variant surface glycoprotein in Trypanosoma brucei. Mol Microbiol. 2017; 106(4):614-634. PMC: 5698767. DOI: 10.1111/mmi.13838. View

20.

Bitter W, Gerrits H, Kieft R, Borst P . The role of transferrin-receptor variation in the host range of Trypanosoma brucei. Nature. 1998; 391(6666):499-502. DOI: 10.1038/35166. View