HBZ and its roles in HTLV-1 oncogenesis

Abstract

HumanT-cell leukemia virus type 1 (HTLV-1) causes adultT-cell leukemia (ATL).The minus strand of HTLV-1 provirus encodes a bZIP protein donated as HTLV-1 bZIP factor (HBZ). Among the HTLV-1 regulatory and accessory genes, the tax and HBZ genes were thought to play critical roles in oncogenesis. However, HBZ is the only gene that remains intact and is consistently expressed in all ATL cases, w′hile the tax gene is frequently inactivated by epigenetic modifications or deletion of the 5′ LTR. HBZ gene promotes the proliferation of ATL cells through its mRNA form. Moreover, HBZ inducesT-cell lymphoma and′systemic inflammation in vivo. HBZ fulfills its functions mainly through regulating HTLV-1 5 LTR transcription and modulating a variety of cellular signaling pathways which are related with cell growth, immune response, and T-cell differentiation.Taken together, the multiple functions of HBZ render its predominant function in leukemogenesis of ATL. © 2012 Zhao and Matsuoka.