Matsuoka Masao
Institute for Virus Research, Kyoto University, Kyoto, Japan.
Gan To Kagaku Ryoho. 2010 Jan;37(1):10-3.
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.
人类T细胞白血病病毒1型（HTLV-1）是成人T细胞白血病（ATL）的病原体。HTLV-1经过漫长的潜伏期后诱发ATL。先前的研究表明了tax基因的重要性。然而，在大约一半的ATL病例中，Tax通过三种机制不表达：1）5'长末端重复序列（LTR）缺失，2）5'LTR的DNA甲基化，以及3）tax基因的基因变化。我们发现，在所有ATL病例中，HTLV-1碱性亮氨酸拉链因子（HBZ）基因编码区和3'LTR均保持完整。HBZ基因在所有ATL病例中均有表达，其表达促进ATL细胞增殖。HBZ与包括c-Jun、JunB、JunD和p65在内的多种宿主因子相互作用。因此，HBZ除了促进增殖外，还调节细胞信号通路。这些发现表明，HBZ是HTLV-1致癌的必需病毒基因。
