Lab. de Imunologia Básica e Aplicada, Depto. of Immunology, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Unidade de Espectrometria de Massas e Proteômica (UEMP), Instituto de Bioquímica Médica Leopoldo de Meis and Instituto Nacional de Biologia Estrutural e Bioimagem (INBEB), UFRJ, Rio de Janeiro, RJ, Brazil.
Sci Rep. 2018 Sep 25;8(1):14354. doi: 10.1038/s41598-018-32324-2.
Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The endothelial breakdown and migration of leukocytes, including monocytes, to the spinal cord are involved in HAM/TSP development. Monocytes from HTLV-1-infected individuals exhibit important functional differences when compared to cells from uninfected donors. Using proteomic shot gun strategy, performed by nanoACQUITY-UPLC system, we analyzed monocytes isolated from peripheral blood of asymptomatic carriers (AC), HAM/TSP and uninfected individuals. 534 proteins were identified among which 376 were quantified by Expression software. Our study revealed a panel of changes in protein expression linked to HTLV-1 infection. Upregulation of heat shock proteins and downregulation of canonical histone expression were observed in monocytes from HTLV-1-infected patients. Moreover, expression of cytoskeleton proteins was increased in monocytes from HTLV-1-infected patients, mainly in those from HAM/TSP, which was confirmed by flow cytometry and fluorescence microscopy. Importantly, functional assays demonstrated that monocytes from HAM/TSP patients present higher ability for adhesion and transmigration thought endothelium than those from AC and uninfected individuals. The major changes on monocyte protein profile were detected in HAM/TSP patients, suggesting that these alterations exert a relevant role in the establishment of HAM/TSP.
人类 T 细胞嗜淋巴细胞病毒 1 型（HTLV-1）是 HTLV-1 相关脊髓病/热带痉挛性截瘫（HAM/TSP）的病因。内皮细胞的破坏和白细胞（包括单核细胞）向脊髓的迁移参与了 HAM/TSP 的发展。与未感染供体的细胞相比，来自 HTLV-1 感染个体的单核细胞表现出重要的功能差异。使用由 nanoACQUITY-UPLC 系统执行的蛋白质组学 Shot Gun 策略，我们分析了来自无症状携带者（AC）、HAM/TSP 和未感染个体的外周血单核细胞。在鉴定的 534 种蛋白质中，有 376 种通过 Expression software 进行了定量。我们的研究揭示了与 HTLV-1 感染相关的一组蛋白质表达变化。在 HTLV-1 感染患者的单核细胞中观察到热休克蛋白的上调和经典组蛋白表达的下调。此外，在 HTLV-1 感染患者的单核细胞中，细胞骨架蛋白的表达增加，主要在 HAM/TSP 患者中，这通过流式细胞术和荧光显微镜得到了证实。重要的是，功能测定表明，与 AC 和未感染个体相比，来自 HAM/TSP 患者的单核细胞具有更高的粘附和穿过内皮的能力。在 HAM/TSP 患者中检测到单核细胞蛋白谱的主要变化，表明这些改变在 HAM/TSP 的建立中发挥了相关作用。
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