Fig. 4.

The proposed signalling network which occurs during HAM/TSP based on the hub genes. Induction with death receptors (i.e. Fas, TNFR and PD-1) causes apoptosis and cytotoxic enzymes, and activation of IRF1 leads to activation of caspase cascade and cell death. By contrast, CD28, TCR, and the cytokine receptor signal network influence PI3K-Akt, mTOR, NF_κB, CREB, BH3-Only family activation as well as inhibition of cyclin-dependent kinases, which promote cell survival and T cell proliferation. In addition, HTLV-1 virulence factors, particularly Tax and HBZ, can support T cell proliferation using various signalling pathways which prevent apoptosis activation.