布氏锥虫抗原变异的体内动力学
The in vivo dynamics of antigenic variation in Trypanosoma brucei.
作者信息
Mugnier Monica R, Cross George A M, Papavasiliou F Nina
机构信息
Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY, USA. Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA.
出版信息
Science. 2015 Mar 27;347(6229):1470-3. doi: 10.1126/science.aaa4502.
Abstract
Trypanosoma brucei, a causative agent of African Sleeping Sickness, constantly changes its dense variant surface glycoprotein (VSG) coat to avoid elimination by the immune system of its mammalian host, using an extensive repertoire of dedicated genes. However, the dynamics of VSG expression in T. brucei during an infection are poorly understood. We have developed a method, based on de novo assembly of VSGs, for quantitatively examining the diversity of expressed VSGs in any population of trypanosomes and monitored VSG population dynamics in vivo. Our experiments revealed unexpected diversity within parasite populations and a mechanism for diversifying the genome-encoded VSG repertoire. The interaction between T. brucei and its host is substantially more dynamic and nuanced than previously expected.
摘要
布氏锥虫是非洲昏睡病的病原体，它利用大量专门基因不断改变其致密的可变表面糖蛋白（VSG）外壳，以避免被其哺乳动物宿主的免疫系统清除。然而，在感染过程中布氏锥虫中VSG表达的动态变化却知之甚少。我们基于VSG的从头组装开发了一种方法，用于定量检测任何锥虫群体中表达的VSG的多样性，并在体内监测VSG群体动态。我们的实验揭示了寄生虫群体中意想不到的多样性以及使基因组编码的VSG库多样化的机制。布氏锥虫与其宿主之间的相互作用比以前预期的要更加动态和微妙。
相似文献
1
The in vivo dynamics of antigenic variation in Trypanosoma brucei.
Science. 2015 Mar 27;347(6229):1470-3. doi: 10.1126/science.aaa4502.
2
A Host-Pathogen Interaction Reduced to First Principles: Antigenic Variation in T. brucei.
Results Probl Cell Differ. 2015;57:23-46. doi: 10.1007/978-3-319-20819-0_2.
3
Application of long read sequencing to determine expressed antigen diversity in Trypanosoma brucei infections.
PLoS Negl Trop Dis. 2019 Apr 3;13(4):e0007262. doi: 10.1371/journal.pntd.0007262. eCollection 2019 Apr.
4
VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains.
mBio. 2022 Dec 20;13(6):e0255322. doi: 10.1128/mbio.02553-22. Epub 2022 Nov 10.
5
Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation.
Nat Commun. 2017 Oct 10;8(1):828. doi: 10.1038/s41467-017-00959-w.
6
Trypanosomes expressing a mosaic variant surface glycoprotein coat escape early detection by the immune system.
Infect Immun. 2005 May;73(5):2690-7. doi: 10.1128/IAI.73.5.2690-2697.2005.
7
African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system.
Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20725-20735. doi: 10.1073/pnas.1905120116. Epub 2019 Sep 25.
8
Quantitative sequencing confirms VSG diversity as central to immune evasion by Trypanosoma brucei.
Trends Parasitol. 2015 Aug;31(8):346-9. doi: 10.1016/j.pt.2015.05.001. Epub 2015 May 18.
9
Critical interplay between parasite differentiation, host immunity, and antigenic variation in trypanosome infections.
Am Nat. 2010 Oct;176(4):424-39. doi: 10.1086/656276.
10
Variant antigen diversity in Trypanosoma vivax is not driven by recombination.
Nat Commun. 2020 Feb 12;11(1):844. doi: 10.1038/s41467-020-14575-8.
引用本文的文献
1
The molecular basis of coordinated antigen switching enabling chronic infection by human malaria parasites.
bioRxiv. 2025 Jul 16:2025.07.16.665170. doi: 10.1101/2025.07.16.665170.
2
Detection of antibodies against the African parasite Trypanosoma brucei using synthetic glycosylphosphatidylinositol oligosaccharide fragments.
Glycoconj J. 2025 Jun 24. doi: 10.1007/s10719-025-10186-x.
3
Structure-function analysis defines the minimal functional C-terminal domain of the variant surface glycoprotein of Trypanosomabrucei.
J Biol Chem. 2025 May 22;301(7):110260. doi: 10.1016/j.jbc.2025.110260.
4
Genomic determinants of antigen expression hierarchy in African trypanosomes.
Nature. 2025 Mar 12. doi: 10.1038/s41586-025-08720-w.
5
Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei.
Nature. 2024 Dec;636(8042):430-437. doi: 10.1038/s41586-024-08151-z. Epub 2024 Oct 30.
6
DNA damage drives antigen diversification through mosaic Variant Surface Glycoprotein (VSG) formation in .
bioRxiv. 2024 Aug 30:2024.03.22.582209. doi: 10.1101/2024.03.22.582209.
7
Identifying Antigenic Switching by Clonal Cell Barcoding and Nanopore Sequencing in .
Bio Protoc. 2023 Dec 20;13(24):e4904. doi: 10.21769/BioProtoc.4904.
8
Mitigation of Trypanosoma congolense-Associated Anemia and Expression of Trans-sialidase (TconTS) Gene Variants by Eugenol.
Acta Parasitol. 2024 Mar;69(1):384-395. doi: 10.1007/s11686-023-00750-6. Epub 2023 Dec 26.
9
PI(3,4,5)P3 allosteric regulation of repressor activator protein 1 controls antigenic variation in trypanosomes.
Elife. 2023 Nov 29;12:RP89331. doi: 10.7554/eLife.89331.
10
Therapeutic efficacy of β-sitosterol treatment on infection, anemia development, and trans-sialidase () gene expression.
Front Microbiol. 2023 Sep 27;14:1282257. doi: 10.3389/fmicb.2023.1282257. eCollection 2023.
本文引用的文献
1
Capturing the variant surface glycoprotein repertoire (the VSGnome) of Trypanosoma brucei Lister 427.
Mol Biochem Parasitol. 2014 Jun;195(1):59-73. doi: 10.1016/j.molbiopara.2014.06.004. Epub 2014 Jun 30.
2
IgG variable region and VH CDR3 diversity in unimmunized mice analyzed by massively parallel sequencing.
Mol Immunol. 2014 Feb;57(2):274-83. doi: 10.1016/j.molimm.2013.09.008. Epub 2013 Nov 8.
3
Identification of Trypanosome proteins in plasma from African sleeping sickness patients infected with T. b. rhodesiense.
PLoS One. 2013 Aug 8;8(8):e71463. doi: 10.1371/journal.pone.0071463. eCollection 2013.
4
Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation.
PLoS Pathog. 2013;9(7):e1003502. doi: 10.1371/journal.ppat.1003502. Epub 2013 Jul 11.
5
Efficient and comprehensive representation of uniqueness for next-generation sequencing by minimum unique length analyses.
PLoS One. 2013;8(1):e53822. doi: 10.1371/journal.pone.0053822. Epub 2013 Jan 18.
6
Linking the antigen archive structure to pathogen fitness in African trypanosomes.
Proc Biol Sci. 2013 Jan 2;280(1753):20122129. doi: 10.1098/rspb.2012.2129. Print 2013 Feb 22.
7
CD-HIT: accelerated for clustering the next-generation sequencing data.
Bioinformatics. 2012 Dec 1;28(23):3150-2. doi: 10.1093/bioinformatics/bts565. Epub 2012 Oct 11.
8
Full-length transcriptome assembly from RNA-Seq data without a reference genome.
Nat Biotechnol. 2011 May 15;29(7):644-52. doi: 10.1038/nbt.1883.
9
Transmission stages dominate trypanosome within-host dynamics during chronic infections.
Cell Host Microbe. 2011 Apr 21;9(4):310-8. doi: 10.1016/j.chom.2011.03.013.
10
Bioluminescent imaging of Trypanosoma brucei shows preferential testis dissemination which may hamper drug efficacy in sleeping sickness.
PLoS Negl Trop Dis. 2009 Jul 21;3(7):e486. doi: 10.1371/journal.pntd.0000486.
Zotero 插件