Review Article Aberration in Signal Transduction Pathway in Human T-Cell Leukemia Virus Type I-Infected T Cells

Adult T-cell leukemia (ATL) is a fatal T-lymphoproliferative disorder, and its development is associated with infection by human T-cell leukemia virus type I (HTLV-I). The molecular mechanism of leukemogenesis has not yet been elucidated. However, several studies have suggested that aberrations in signal transduction in virus-infected T cells are involved in the development of the disease. For instance, NF-ﾎｺB/Rel, AP-1, and Jak/STAT signaling pathways are transiently activated in normal T cells by growth-signals, whereas they are constitutively deployed in HTLV-I-infected T-cell lines. The HTLV-I viral transactivator Tax has oncogenic properties, and is a key molecule in ATL development. Tax activates several transcription factors, including NF-ﾎｺB/Rel and AP-1 in HTLV-I-transformed T-cell lines, and induces the expression of STAT proteins. Unlike HTLV-I-transformed T-cell lines, primary ATL cells express low levels of Tax protein. Nevertheless, the NF-ﾎｺB/Rel, AP-1, and Jak/STAT signaling pathways in primary ATL cells are also constitutively activated. Thus, the aberration in signal transduction pathway may be a common key factor to prolonged survival and proliferation of HTLV-Iinfected T cells in vitro and in vivo, but the mechanisms seem to be different. Aberration in signal transduction could be targeted for the therapeutic control of HTLV-I-associated disease