ArticleNature microbiology2018
African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.
Article in Nature microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
- The major diagnostic VSG LiTat 1.3 of the human parasite Trypanosoma brucei gambiense is a trimer in solution.PLoS pathogens · 2026Article
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- Prion Protein-Derived Cell-Penetrating Peptide Inhibits Type II Diabetes-Associated Islet Amyloid Polypeptide Aggregation and Cytotoxicity.Biochemistry · 2026Article
- Key Regulators of Parasite Biology Viewed Through a Post-Translational Modification Repertoire.Proteomics · 2025Review
- Targets of the human antibody response to the variant surface glycoprotein ofbioRxiv : the preprint server for biology · 2025Article
- Detection of antibodies against the African parasite Trypanosoma brucei using synthetic glycosylphosphatidylinositol oligosaccharide fragments.Glycoconjugate journal · 2025Article
- Evasive mechanisms of human VSG and PfEMP1 antigens with link to Vaccine scenario: a review.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Review
- Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals.Cell surface (Amsterdam, Netherlands) · 2024Article
- Beyond the VSG layer: Exploring the role of intrinsic disorder in the invariant surface glycoproteins of African trypanosomes.PLoS pathogens · 2024Article
- A structural classification of the variant surface glycoproteins of the African trypanosome.PLoS neglected tropical diseases · 2023Article
- Competition among variants is predictable and contributes to the antigenic variation dynamics of African trypanosomes.PLoS pathogens · 2023Article
- Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.Nature communications · 2023Article
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- Structural similarities between the metacyclic and bloodstream form variant surface glycoproteins of the African trypanosome.PLoS neglected tropical diseases · 2023Article
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- Common and unique features of glycosylation and glycosyltransferases in African trypanosomes.The Biochemical journal · 2022Article
- Genetic and immunological basis of human African trypanosomiasis.Current opinion in immunology · 2021Review
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- The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples.Pathogens (Basel, Switzerland) · 2021Article
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12 authors at 4 institutions in 3 countries.
Funding
Abstract
The African trypanosome Trypanosoma brucei spp. is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity. The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs. This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture. We establish here that this model does not account for the scope of VSG structural and biochemical diversity. The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state. The structure also reveals an O-linked carbohydrate on the top surface of VSG3. Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs. We demonstrate that this O-glycosylation increases parasite virulence by impairing the generation of protective immunity. These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.