Coevolution of HTLV-1-HBZ, Tax, and proviral load with host IRF-1 and CCNA-2 in HAM/TSP patients

Abstract

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.