Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran.
Infect Genet Evol. 2022 Sep;103:105337. doi: 10.1016/j.meegid.2022.105337. Epub 2022 Jul 12.
Background HTLV-1-associated myelopathy (HAM/TSP) is a progressive neurodegenerative inflammatory condition of HTLV-1 infection. Viral-host interactions are a significant contributor to the symptoms of HTLV-1-associated diseases. Therefore, in this study, the expression of the main regulatory viral factors and proviral load (PVL) and two host transcription molecules were evaluated in HAM/TSP patients. Materials and methods The study population included 17 HAM/TSP patients, 20 asymptomatic carriers (ACs), and 19 healthy controls (HCs). RNA and DNA were extracted from PBMCs for assessment of the gene expressions and PVL assessment using RT-qPCR and TaqMan method. Results HTLV-1-PVL was higher in HAM/TSPs (395.80 ± 99.69) than ACs (92.92 ± 29.41) (P = 0.001). The Tax expression in HAM/TSPs (7.8 ± 5.7) was strongly higher than ACs (0.06 ± 0.04) (P = 0.02), while HTLV-1-HBZ was only increased around three times in HAM/TSPs (3.17), compared to ACs (1.20) and not significant. The host IRF1 expression in HAM/TSPs (0.4 ± 0.31) was higher than ACs (0.09 ± 0.05) (P = 0.02) and also HCs (0.16 ± 0.07) (P = 0.5), but lower in ACs than HCs (p = 0.01). Although, in HAM/TSPs (0.13 ± 0.09) and ACs (0.03 ± 0.02) CCNA-2 expression was statistically fewer than HCs (0.18 ± 0.06) (P = 0.03, P = 0.001, respectively), in HAM/TSP was higher than ACs (P = 0.1), but did not meet a 95% confidence interval. Conclusion The study showed that HTLV-1-PVL and Tax, along with host IRF-1, could be considered biomarkers in HAM/TSP development. Furthermore, IRF-1, as an essential transcription factor, can be considered a pivotal target in HAM/TSPs treatment.
人类嗜 T 淋巴细胞病毒 1 相关性脊髓病(HAM/TSP)是一种由人类嗜 T 淋巴细胞病毒 1 感染引起的进行性神经退行性炎症疾病。病毒-宿主相互作用是人类嗜 T 淋巴细胞病毒 1 相关性疾病症状的重要贡献者。因此,在这项研究中,评估了 HAM/TSP 患者中主要调节病毒因子和前病毒载量(PVL)以及两个宿主转录分子的表达。
研究人群包括 17 名 HAM/TSP 患者、20 名无症状携带者(ACs)和 19 名健康对照(HCs)。从 PBMC 中提取 RNA 和 DNA,用于使用 RT-qPCR 和 TaqMan 方法评估基因表达和 PVL 评估。
HAM/TSP 患者的 HTLV-1-PVL (395.80 ± 99.69)高于 ACs (92.92 ± 29.41)(P = 0.001)。HAM/TSP 患者中的 Tax 表达(7.8 ± 5.7)明显高于 ACs (0.06 ± 0.04)(P = 0.02),而 HTLV-1-HBZ 仅在 HAM/TSP 中增加了三倍左右(3.17),与 ACs (1.20)相比无显著差异。HAM/TSP 患者的宿主 IRF1 表达(0.4 ± 0.31)高于 ACs (0.09 ± 0.05)(P = 0.02)和 HCs (0.16 ± 0.07)(P = 0.5),但低于 ACs (p = 0.01)。尽管 HAM/TSP 患者(0.13 ± 0.09)和 ACs (0.03 ± 0.02)的 CCNA-2 表达明显低于 HCs (0.18 ± 0.06)(P = 0.03,P = 0.001),但在 HAM/TSP 中高于 ACs (P = 0.1),但未达到 95%置信区间。
该研究表明,HTLV-1-PVL 和 Tax 以及宿主 IRF-1 可被视为 HAM/TSP 发展的生物标志物。此外,IRF-1 作为一种重要的转录因子,可被视为 HAM/TSP 治疗的关键靶点。