The effect of HTLV-1 virulence factors (HBZ, Tax, proviral load), HLA class I and plasma neopterin on manifestation of HTLV-1 associated myelopathy tropical spastic paraparesis.

Previous studies have suggested debatable roles of Tax and HBZ gene expression in the pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this study, HTLV-1 and host interactions in the manifestation of HAM/TSP were evaluated. A cross-sectional study was conducted on 33 HAM/TSP patients and 38 HTLV-1 asymptomatic carriers (ACs). HTLV-1-Tax, HBZ gene expression, and proviral load (PVL) were assessed using the quantitative real-time PCR (TaqMan), host plasma neopterin level, and HLA-I, and the clinical manifestation were evaluated. The HTLV-1 PVLs in HAM/TSP and ACs were 306±360.741 copies/104 PBMCs and 250.98±629.94 copies/104 PBMCs, respectively; the PVL was higher in HAM/TSP than that in ACs (p=0.004). HTLV-1 Tax and HBZ expression in HAM/TSP was higher than that in ACs, wherein only the Tax expression was statistically significant (p=0.039). In contrast to Japanese HTLV-1-infected subjects, HLA-A*02, HLA-A*24, HLA-Cw*08, and HLA-B*5401 did not exhibit preventive effects for HAM/TSP manifestation. The plasma neopterin level was significantly higher in HAM/TSPs than that in ACs; furthermore, there was a strong significant correlation between plasma neopterin and PVL (R=0.76, p=0.001). Moreover, there were significant correlation between urinary disturbances and haematological indices, including the RBC count (R=-0.61, p=0.01) and Hematocrit (Ht) index (R=-0.75, p=0.002), and between mobility disturbances with Tax expression (R=-0.58, p=0.02) and WBC counts (R=-0.54, p=0.04), and finally, a significant association was found between the sensory disturbances and PVL (p=0.05). Overall, HTLV-1 PVL and Tax may be the valid predictors of disease development, and the neopterin level may be a valid predictor of disease progression. In addition, Tax and neopterin are more helpful than PVL for the monitoring of HTLV-1-infected patients.

Tarokhian H ，Taghadosi M ，Rafatpanah H ，Rajaei T ，Azarpazhooh MR ，Valizadeh N ，Rezaee SAR ... -  《-》

The IL-18, IL-12, and IFN-γ expression in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, HTLV-1 carriers, and healthy subjects.

Bidkhori HR ，Hedayati-Moghaddam MR ，Mosavat A ，Valizadeh N ，Tadayon M ，Ahmadi Ghezeldasht S ，Rafatpanah H ，Rezaee SA ... -  《-》

Evaluation of HTLV-1 HBZ and proviral load, together with host IFN λ3, in pathogenesis of HAM/TSP.

Human T-cell lymphotropic virus 1 (HTLV-1) is associated with two progressive diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although HTLV-1 proviral load (PVL) has been introduced as a risk factor for these diseases' progression, it is not sufficient on its own to yield an accurate estimation of the outcome of the infection. In the present study, PVL and HTLV-1 basic leucine zipper factor (HBZ) expression level as viral factors, and IFN λ3 as a host factor, were evaluated in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs). During 2014-2015, 12 HAM/TSP patients and 18 ACs who had been referred to the HTLV-1 Clinic, Ghaem Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and the DNA and mRNA were extracted for quantification of HBZ, IFN λ3 expression, and PVL using real-time PCR (TaqMan method). Although the PVL was higher in the HAM/TSP group, with a 94% confidence interval, there were no considerable differences in terms of HBZ mRNA and PVL between ACs and HAM patients. IFN λ3 expression in the HAM/TSP group was significantly higher than in the ACs (P = 0.02). To the best of our knowledge, no study has evaluated the expression level of IFN λ3 in HTLV-1 positive patients. The immune response against HTLV-1 viral antigens and virulent factors will therefore further refine our knowledge of interactions between the virus and host in the pathogenesis of HTLV-1-related disorders. The virus PVL and the host IFN λ3 can be used as pathogenic factors of HTLV-1 infected patients at risk of HAM/TSP manifestation. J. Med. Virol. 89:1102-1107, 2017. © 2016 Wiley Periodicals, Inc.

Mozhgani SH ，Jaberi N ，Rezaee SA ，Bustani R ，Jazayeri SM ，Akbarin MM ，Milani S ，Tarokhian H ，Norouzi M ... -  《-》

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

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.

Saffari M ，Rahimzada M ，Mirhosseini A ，Ghezaldasht SA ，Valizadeh N ，Moshfegh M ，Moradi MT ，Rezaee SA ... -  《-》

HTLV-1-host interactions on the development of adult T cell leukemia/lymphoma: virus and host gene expressions.

Tarokhian H ，Rahimi H ，Mosavat A ，Shirdel A ，Rafatpanah H ，Akbarin MM ，Bari A ，Ramezani S ，Rezaee SA ... -  《BMC CANCER》