Trypanosoma brucei gambiense is the primary causative agent of human African trypanosomiasis (HAT), a vector-borne disease endemic to West and Central Africa. The extracellular parasite evades antibody recognition within the host bloodstream by altering its Variant Surface Glycoprotein (VSG) coat through a process of antigenic variation. The serological tests which are widely used to screen for HAT use VSG as one of the target antigens. However, the VSGs expressed during human infection have not been characterized. Here we use VSG-seq to analyze the VSGs expressed in the blood of patients infected with T. b. gambiense and compared them to VSG expression in T. b. rhodesiense infections in humans as well as T. b. brucei infections in mice. The 44 VSGs expressed during T. b. gambiense infection revealed a striking bias towards expression of type B N-termini (82% of detected VSGs). This bias is specific to T. b. gambiense, which is unique among T. brucei subspecies in its chronic clinical presentation and anthroponotic nature, pointing towards a potential link between VSG expression and pathogenesis. The expressed T. b. gambiense VSGs also share very little similarity to sequences from 36 T. b. gambiense whole genome sequencing datasets, particularly in areas of the VSG protein exposed to host antibodies, suggesting that wild T. brucei VSG repertoires vary more than previously expected. Overall, this work demonstrates new features of antigenic variation in T. brucei gambiense and highlights the importance of understanding VSG repertoires in nature.

中文翻译：

---

在自然结核病期间表达的 VSG。冈比亚感染表现出广泛的序列差异和亚种特异性表达偏差

冈比亚布氏锥虫是人类非洲锥虫病 (HAT) 的主要病原体，该病是西非和中非特有的媒介传播疾病。胞外寄生虫通过抗原变异过程改变其变异表面糖蛋白 (VSG) 外壳，从而逃避宿主血流中的抗体识别。广泛用于筛查 HAT 的血清学测试使用 VSG 作为靶抗原之一。然而，在人类感染期间表达的VSG尚未表征。在这里，我们使用 VSG-seq 来分析T. b.感染患者血液中表达的VSG 。gambiense并将它们与T. b. 中的 VSG 表达进行比较。人类的罗得西亚感染以及T. B. 布鲁氏菌感染小鼠。在T. b.期间表达的 44 个VSG 。冈比亚感染揭示了对 B 型 N 末端表达的显着偏见（检测到的 VSG 的 82%）。这种偏见是T. b. 特有的。gambiense ，它在T. brucei亚种中的慢性临床表现和人类学性质是独一无二的，指出VSG表达和发病机制之间的潜在联系。表达的T. b. 冈比亚 VSG与来自 36 T. b.的序列也几乎没有相似之处。冈比亚全基因组测序数据集，特别是在暴露于宿主抗体的 VSG 蛋白区域，表明野生T. brucei VSG曲目的变化比以前预期的要大。总体而言，这项工作展示了T. brucei gambiense抗原变异的新特征，并强调了了解自然界中VSG库的重要性。