The Effect of HTLV-1 Virulence Factors (HBZ, Tax, Proviral Load), and Expression of CXCR3 and CCR6 and Their Ligands on Manifestation of HTLV-1 Associated Myelopathy Tropical Spastic Paraparesis

Previous studies have suggested debatable roles of Tax and HBZ gene expression as virus factors and chemokines and chemokine receptorsin host for induction of inflammatory response in HTLV- 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In the present study HTLV-1 and host interactions, chemokine and chemokine receptors involved in trafficking of lymphocytes to the CNS weremeasured. Materials and Methods: A cross-sectional study was conducted on 33 HAM/TSP patients and 38 HTLV-1 asymptomatic carriers (ACs). Proviral load (PVL) were assessed using the quantitative real-time PCR (TaqMan), HTLV-1-Tax, HBZ gene expression,and, CCR6, and CXCR3 mRNA expression, and CXCL9 and CXCL10 protein levels and HLA-I were evaluated. Results: 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 notexhibit preventive effects for HAM/TSP manifestation. CCR6 expression was higher in HAM/TSP patients and in ACs compared to the healthy controls (P = 0.005 and P = 0.04, respectively). A significant difference was observed in CCR6 expression when a combinationof HAM/TSP patients and ACs were compared to the healthy individuals (P = 0.005). Furthermore, there was a significantly lower CXCR3 expression between HAM/TSP and control groups (P = 0.001), and between the ACs and healthy controls (P = 0.001). However,the increased CXCR3 expression in ACs compared to HAM/TSP patients was not significant. Furthermore, the CXCL10 protein levels in HAM/TSP patients was higher than in controls (P = 0.012), and CXCL9 protein levels was also higher in the HAM/TSP and ACs groups than in the controls (P = 0.001 and P = 0.004, respectively). Conclusion: Overall, HTLV-1 PVL and Tax may be the valid predictors of disease development,but Tax is more helpful than PVL for the monitoring of HTLV-1-infected patients. It seems that decreased expression of CXCR3 and higher expression of CCR6 were associated with HTLV-1 infection, what indicate that these alterations may favor virus dissemination butnot disease manifestation.