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与 HAM/TSP 患者相比,HTLV-1 感染的无症状携带者过度表达凋亡和细胞毒性相关分子。

HTLV-1-infected asymptomatic carriers compared to HAM/TSP patients over-express the apoptosis- and cytotoxicity-related molecules.

机构信息

Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Med Microbiol Immunol. 2019 Dec;208(6):835-844. doi: 10.1007/s00430-019-00625-6. Epub 2019 Jul 18.

Abstract

HTLV-1 infection causes a chronic progressive debilitating neuroinflammatory disease which is called, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). One of the host defense mechanisms against viral infection is apoptosis which may control HTLV-1 infection. Therefore, we aimed to investigate this process and its interaction with viral factors in HTLV-1-infected asymptomatic carriers (ACs) compared to HAM/TSP patients. Fas, FasL, TRAIL, perforin, granzyme A, granzyme B, and granulysin gene expression and serum levels of Fas, FasL, TRAIL, and granulysin in the peripheral blood of 21 sex- and age-matched healthy controls (HCs), ACs, and HAM/TSP patients were evaluated. Also, the level of granulysin secretion in the cell culture supernatant was measured. Finally, the correlation of the expression of these molecules with HTLV-1 proviral load (PVL), Tax, and HBZ mRNA expression was analyzed. ACs compared to HAM/TSP patients significantly over-expressed the Fas, FasL, TRAIL, perforin, and granzyme B molecules. Fas, FasL, TRAIL, and granulysin serum levels were not different among studied groups; whereas, the secretion of granulysin was significantly decreased in ACs and HAM/TSP patients compared to HCs. Also, HAM/TSP patients expressed higher levels of HTLV-1 PVL, Tax, and HBZ mRNA. In addition, in ACs, inverse correlations between the Fas, FasL, TRAIL, perforin, granzyme B, and granulysin levels with HBZ mRNA expression were seen. ACs compared to HAM/TSP patients over-expressed the apoptosis- and cytotoxicity-related molecules. It could be concluded that successful control of the HTLV-1 infection and suppression of HAM/TSP development stem from the strong apoptosis and cytotoxic activity in the peripheral blood of ACs.

摘要

人类嗜 T 淋巴细胞病毒 1 (HTLV-1)感染会导致一种慢性进行性、使人虚弱的神经炎症性疾病,即人类嗜 T 淋巴细胞病毒 1 相关性脊髓病/热带痉挛性截瘫(HAM/TSP)。细胞凋亡是宿主防御病毒感染的机制之一,它可能可以控制 HTLV-1 的感染。因此,我们旨在研究这一过程及其与 HTLV-1 感染无症状携带者(ACs)与 HAM/TSP 患者的病毒因子的相互作用。我们评估了 21 名年龄和性别匹配的健康对照者(HCs)、ACs 和 HAM/TSP 患者的外周血中 Fas、FasL、TRAIL、穿孔素、颗粒酶 A、颗粒酶 B 和颗粒溶素基因表达和 Fas、FasL、TRAIL 和颗粒溶素的血清水平,同时测量了细胞培养上清液中颗粒溶素的分泌水平。最后,分析了这些分子的表达与 HTLV-1 前病毒载量(PVL)、Tax 和 HBZ mRNA 表达的相关性。与 HAM/TSP 患者相比,ACs 明显过表达 Fas、FasL、TRAIL、穿孔素和颗粒酶 B 分子。研究组之间 Fas、FasL、TRAIL 和颗粒溶素的血清水平没有差异;然而,与 HCs 相比,ACs 和 HAM/TSP 患者的颗粒溶素分泌明显减少。此外,HAM/TSP 患者表达更高水平的 HTLV-1 PVL、Tax 和 HBZ mRNA。此外,在 ACs 中,Fas、FasL、TRAIL、穿孔素、颗粒酶 B 和颗粒溶素水平与 HBZ mRNA 表达呈负相关。与 HAM/TSP 患者相比,ACs 过表达细胞凋亡和细胞毒性相关分子。由此可以得出结论,ACs 外周血中强烈的细胞凋亡和细胞毒性活性可能成功控制了 HTLV-1 感染并抑制了 HAM/TSP 的发展。

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