Institut Pasteur, Université de Paris, Trypanosome Molecular Biology, Department of Parasites and Insect Vectors, Paris, France.
Université de Paris, Sorbonne Paris Cité, Paris, France.
PLoS Pathog. 2021 Nov 12;17(11):e1010038. doi: 10.1371/journal.ppat.1010038. eCollection 2021 Nov.
Antigenic variation is an immune evasion strategy used by Trypanosoma brucei that results in the periodic exchange of the surface protein coat. This process is facilitated by the movement of variant surface glycoprotein genes in or out of a specialized locus known as bloodstream form expression site by homologous recombination, facilitated by blocks of repetitive sequence known as the 70-bp repeats, that provide homology for gene conversion events. DNA double strand breaks are potent drivers of antigenic variation, however where these breaks must fall to elicit a switch is not well understood. To understand how the position of a break influences antigenic variation we established a series of cell lines to study the effect of an I-SceI meganuclease break in the active expression site. We found that a DNA break within repetitive regions is not productive for VSG switching, and show that the break position leads to a distinct gene expression profile and DNA repair response which dictates how antigenic variation proceeds in African trypanosomes.
抗原变异是布氏锥虫（Trypanosoma brucei）采用的一种免疫逃避策略，导致表面蛋白被周期性替换。该过程由变异表面糖蛋白基因在同源重组的作用下，在一个称为血流形式表达位点的特殊基因座内或外移动来完成，该过程由称为 70-bp 重复的重复序列块提供同源性，以促进基因转换事件。DNA 双链断裂是抗原变异的有力驱动因素，然而，引发这种变化的断裂位置尚不清楚。为了了解断裂的位置如何影响抗原变异，我们建立了一系列细胞系来研究 I-SceI 核酸内切酶在活跃表达位点的断裂的影响。我们发现重复区域内的 DNA 断裂对 VSG 转换没有效果，并表明断裂位置导致了一个独特的基因表达谱和 DNA 修复反应，从而决定了抗原变异在非洲锥虫中的进展。
