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锥虫 vivax 变异抗原多样性不受重组驱动。

Variant antigen diversity in Trypanosoma vivax is not driven by recombination.

机构信息

Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, 146 Brownlow Hill, Liverpool, L3 5RF, UK.

Department of Veterinary Pathology, Faculty of Agrarian and Veterinary Sciences, São Paulo State University (UNESP), Jaboticabal, SP, Brazil.

出版信息

Nat Commun. 2020 Feb 12;11(1):844. doi: 10.1038/s41467-020-14575-8.

DOI:10.1038/s41467-020-14575-8
PMID:32051413
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7015903/
Abstract

African trypanosomes (Trypanosoma) are vector-borne haemoparasites that survive in the vertebrate bloodstream through antigenic variation of their Variant Surface Glycoprotein (VSG). Recombination, or rather segmented gene conversion, is fundamental in Trypanosoma brucei for both VSG gene switching and for generating antigenic diversity during infections. Trypanosoma vivax is a related, livestock pathogen whose VSG lack structures that facilitate gene conversion in T. brucei and mechanisms underlying its antigenic diversity are poorly understood. Here we show that species-wide VSG repertoire is broadly conserved across diverse T. vivax clinical strains and has limited antigenic repertoire. We use variant antigen profiling, coalescent approaches and experimental infections to show that recombination plays little role in diversifying T. vivax VSG sequences. These results have immediate consequences for both the current mechanistic model of antigenic variation in African trypanosomes and species differences in virulence and transmission, requiring reconsideration of the wider epidemiology of animal African trypanosomiasis.

摘要

非洲锥虫(Trypanosoma)是通过其变异表面糖蛋白(VSG)的抗原变异在脊椎动物血液中存活的载体传播的血液寄生虫。对于锥虫布鲁斯氏菌来说,重组,或者更确切地说是分段基因转换,对于 VSG 基因转换和在感染期间产生抗原多样性都是至关重要的。亲缘关系密切的家畜病原体锥虫 vivax 的 VSG 缺乏促进 T. brucei 中基因转换的结构,其抗原多样性的基础机制了解甚少。在这里,我们表明,广泛存在于各种 T. vivax 临床菌株中的物种范围的 VSG 库广泛保守,并且具有有限的抗原库。我们使用变体抗原分析、聚结方法和实验感染来表明重组在多样化 T. vivax VSG 序列方面作用不大。这些结果对非洲锥虫抗原变异的当前机制模型以及毒力和传播方面的物种差异具有直接影响,需要重新考虑动物非洲锥虫病的更广泛流行病学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/06906dc68a68/41467_2020_14575_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/5e1603cc0f63/41467_2020_14575_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/5ec4291af627/41467_2020_14575_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/fb85850378d2/41467_2020_14575_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/b3eb56d9312e/41467_2020_14575_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/06906dc68a68/41467_2020_14575_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/5e1603cc0f63/41467_2020_14575_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/5ec4291af627/41467_2020_14575_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/fb85850378d2/41467_2020_14575_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/b3eb56d9312e/41467_2020_14575_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa78/7015903/06906dc68a68/41467_2020_14575_Fig5_HTML.jpg

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