[Mechanism of oncogenesis by human T-cell leukemia virus type 1].

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL). HTLV-1 induced ATL after a long latent period. Previous studies suggested the significance of the tax gene. However, Tax is not expressed in about half of ATL cases by three mechanisms: 1) deletion of 5 long terminal repeat (LTR), 2) DNA methylation of 5 LTR, and 3) genetic changes of the tax gene. We found that the HTLV-1 bZIP factor (HBZ) gene coding region and 3 LTR remain intact in all ATL cases. The HBZ gene was expressed in all ATL cases and its expression promoting proliferation of ATL cells. HBZ interacts with various host factors, including c-Jun, JunB, JunD, and p65. Thus, HBZ modulates cellular signal pathways in addition to promoted proliferation. These findings indicate that HBZ is an essential viral gene for oncogenesis by HTLV-1.