Human T-Cell Leukemia Virus Type 1 (HTLV-1)

Human T-Cell Leukemia Virus Type 1 (HTLV-1) is the first human retrovirus lacking a cell-derived oncogene yet is more complex than other oncogenic retroviruses. In addition to essential structural and enzymatic genes (gag, pro, pol, and env) shared by all retroviral family members, HTLV-1 encodes a unique pX region, which generates two regulatory (Tax, Rex) and five accessory (HBZ, p30, p12, p13, p8) proteins. Among them, Tax and HBZ affect expression levels of several host genes, thereby playing pivotal roles in leukemogenesis. The modes of action of Tax and HBZ involve a variety of cell signaling pathways including CREB/ATF, NF-κB, and PI3K/AKT that lead to accelerated cell proliferation concurrently with induction of genomic lesions. Tax is no longer expressed in most ATL cases but the growth-promoting activities are taken over by mutated host genes closely associated with Tax functions, while HBZ is constitutively expressed to maintain the transforming phenotype.