Human T-Cell Leukemia Virus Type 1, Cellular Transformation, and Adult T-Cell Leukemia

Human T-cell leukemia virus type 1 (HTLV-1) belongs to the delta type retroviruses, which also include bovine leukemia virus (BLV), human T-cell leukemia virus type 2 (HTLV-2), and simian T-cell leukemia virus (STLV) [1]. HTLV-1 is the first retrovirus that was identified as a causative agent of several human diseases, including adult T-cell leukemia (ATL), HTLV-1 associated myelopathy (HAM)/tropical spastic paraparesis (TSP), and HTLV-1 associated uveitis [2, 3]. ATL is a neoplastic disease of CD4-positive T lymphocytes, which is characterized by pleomorphic tumor cells with hypersegmented nuclei, called “flower cells.” HTLV-1 encodes in its pX regaion a potent oncoprotein, Tax. Tax is a transcriptional activator protein that has been reported to activate and inactivate the transcription of many cellular genes. Ectopic over expression of the HTLV-1 Tax has been found to transforms rodent cells and immortalizes human cells ex vivo [4, 5, 6, 7, 8]. Moreover, transgenic mice engineered to express Tax also form tumors readily [9, 10, 11, 12]. Taken together, these findings strongly support a physiological role for Tax in ATL leukemogenesis. Nevertheless, there are reports that tax transcripts are detected in only ∼40% of transformed ATL cells and that only a small proportion of HTLV-1 carriers (6.6% for males and 2.1% for females in Japan) develop ATL after a long latency period (about 60 years in Japan, and 40 years in Jamaica) from the initial infection [1]. These observations argue that besides Tax, other factors such as additional viral genes, host cell, and immune factors may also contribute to the development of ATL. Compatible with the above thinking, it was recently discovered that the HTLV-1 bZIP factor (HBZ), which is encoded by the minus strand of the provirus, is ubiquitously expressed in all ATL cells and possesses cell proliferative function in T cells [13]. HBZ may also contribute to leukemogenesis. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.