AUTHOR=Zhao Tiejun , Matsuoka Masao 

TITLE=HBZ and its roles in HTLV-1 oncogenesis

JOURNAL=Frontiers in Microbiology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2012.00247

DOI=10.3389/fmicb.2012.00247

ISSN=1664-302X

ABSTRACT=<p>Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-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 <italic>tax</italic> and <italic>HBZ</italic> 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, while the tax gene is frequently inactivated by epigenetic modifications or deletion of the 5’LTR. <italic>HBZ</italic> gene promotes the proliferation of ATL cells through its mRNA form. Moreover, HBZ induces T-cell lymphoma and systemic inflammation <italic>in vivo</italic>. 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.</p>