High IFN-γ/IL-10 Expression Ratio and Increased Frequency of Persistent Human T-Cell Lymphotropic Virus Type 1-Infected Clones Are Associated with Human T-Cell Lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis Development
High IFN-γ/IL-10 Expression Ratio and Increased Frequency of Persistent Human T-Cell Lymphotropic Virus Type 1-Infected Clones Are Associated with Human T-Cell Lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis Development
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DOI：
10.1159/000371766
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发表时间：
2015-01-01
期刊：
影响因子：
4.6
通讯作者：
Andrada-Serpa, Maria Jose
中科院分区：
文献类型：
--
作者：
Espindola, Otavio M.;Oliveira, Lua C.;Andrada-Serpa, Maria Jose
背景/目的：人类 T 细胞嗜淋巴细胞病毒 1 型 (HTLV-1) 是一种导致持续感染的逆转录病毒，只有 0.5-5% 的感染者会出现 HTLV-1 相关的脊髓病/热带痉挛性截瘫 (HAM/TSP)。因此，我们研究了区分 HTLV-1 无症状携带者 (AC) 的参数，以增加发生 HAM/TSP 的机会。方法：我们评估了 HTLV-1 原病毒的整合模式、HTLV-1tax 和 HBZ mRNA 以及 IFN-γ 和 IL-10 mRNA 的相对表达，以及原病毒载量 (PVL) 水平。结果：与 AC 相比，HAM/TSP 患者呈现出更多数量的大型持续性 HTLV-1 携带克隆，并且检测到受感染细胞的 HTLV-1tax 和 HBZ 基因表达水平较低，且与 PVL 呈正相关。此外，与 IL-10 相比，HAM/TSP 患者和具有高 PVL 的 AC 表达更高水平的 IFN-γ mRNA，而具有低 PVL 的 AC 则呈现出平衡的 IFN-γ/IL-10 比率。结论：与病毒基因表达相关的大的持续性 HTLV-1 感染克隆的存在，即使是小水平，也可以刺激 HTLV-1 感染个体的强烈炎症反应。 HAW/TSP 患者和具有高 PVL 的 AC 中 IFN-γ/IL-10 相对表达的高比例支持了这一点，表明这些参数可以帮助识别具有发生 HAM/TSP 高风险的 AC。 (C) 2015 S. Karger AG，巴塞尔
Background/Aims: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes a persistent infection, and only 0.5-5% of infected individuals will develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Therefore, we investigated parameters to discriminate HTLV-1 asymptomatic carriers (ACs) with an increased chance to develop HAM/TSP. Methods: We evaluated integration patterns of HTLV-1 provirus, the relative expression of HTLV-1 tax and HBZ mRNAs and of IFN-gamma and IL-10 mRNAs, in addition to proviral load (PVL) levels. Results: HAM/TSP patients presented a higher number of large persistent HTLV-1-carrying clones compared to ACs, and the expression of the HTLV-1 tax and HBZ genes by infected cells was detected at low levels and correlated positively with PVL. In addition, HAM/TSP patients and ACs with high PVL expressed higher levels of IFN-gamma mRNA in comparison to IL-10, while ACs with low PVL presented an equilibrate IFN-gamma/IL-10 ratio. Conclusions: The presence of large persistent HTLV-1-infected clones in association with viral gene expression, even at small levels, could stimulate the intense inflammatory response in HTLV-1-infected individuals. This was supported by a high ratio of IFN-gamma/IL-10 relative expression in HAW/TSP patients and ACs with high PVL, indicating that these parameters could aid the identification of ACs with a high risk to develop HAM/TSP. (C) 2015 S. Karger AG, Basel