This is important because it provides a better understanding of the function and role of HBZ in downregulating viral transcription and, hence, its contribution to viral latency and persistence <i>in vivo</i>, a process that may ultimately lead to the development of ATL.
Murine ATL models include transgenic animals for the viral proteins Tax and HBZ, knock-outs for key cellular regulators, xenografts and humanized immune-deficient mice.
A long latency period from HTLV-1 infection to ATL onset suggests that not only HTLV-1 proteins, such as Tax and HBZ, but also additional genetic and/or epigenetic events are required for ATL development.
Importantly, we revealed that HTLV-1 bZIP factor (HBZ) protein which is expressed in all ATL cases physically interacts with NRF-1 and inhibits the DNA-binding ability of NRF-1.
HBZ, HTLV-1 basic leucine zipper transcription factor, promotes tumor cell proliferation and disrupts Wnt pathway modulators; however, its role in ATL induced osteolytic bone loss is unknown.
We showed that the expression of miRNAs and Dicer1 were downregulated in cells lines expressing HBZ as well as in fresh CD4 (+) cells from acute ATL patients.
Meanwhile, HBZ is expressed in both untransformed infected cells and ATLL cells and is involved in sustaining cell proliferation and silencing virus expression.
In contrast, repressive modifications are not known to occur on the hbz promoter located in the 3' LTR, and hbz expression has been consistently detected in all ATL patient samples.
The HTLV-1 basic leucine zipper factor (HBZ) gene is encoded in the minus strand of the viral DNA and is constitutively expressed in infected cells and ATL cells.
This method showed that all cases (n = 19) were positive for the ATLL cell line (MT-1, MT-2, and MT-4) and ATLL mouse model (HBZ-Tg mice and NOD/SCID/β2-microglobulin(null) mice with ATLL transplanted), and the HBZ gene was also detected in all human ATLL cases (n = 16).
In most adult T-cell leukemia (ATL) cells, Tax oncoprotein expression is typically low or undetectable, whereas Hbz gene expression is maintained, suggesting that Hbz expression may support infected cell survival and, ultimately, leukemogenesis.