Overall, our findings suggest that both HBZ and Tax1 are negative regulators of immediate early IFN-β innate immune responses, while HBZ but not Tax1 positively regulates the induction of IFN-α and downstream IFN-α signaling.<b>IMPORTANCE</b> Type I interferons are powerful antiviral cytokines and are used extensively in the treatment of HTLV-1-induced adult T cell leukemia (ATL).
Whether NF-κB promoter transactivation by the human T-cell leukemia virus type 1 (HTLV-1) Tax protein requires Tax SUMOylation is still a matter of debate.
The Tax protein is one of the products of the human T-cell leukemia virus type 1 (HTLV-1) which is the etiologic agent of adult T-cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells.
Immunohistochemical staining for Tax protein showed positivity in seven of 11 cases in NOD/SCID/β2-microglobulin(null) mice with ATLL transplanted and in six of eight human ATLL cases, but the percentage of positive cells was very low (range, 1-5%).
Ectopic expression of human T cell leukemia virus 1-encoded Tax protein, which resembles K13 in inducing constitutive NF-κB activation, similarly protected plasmacytoma cells against IL6 withdrawal-induced apoptosis.
At the incipient stages of the development of adult T-cell leukemia, T-cells infected with human T-cell leukemia virus type 1 (HTLV-1) suffer disregulation in cell growth caused by aberrant expression of host genes by the HTLV-1 transactivator protein Tax (Tax1).
Pin1 is highly expressed in adult T-cell leukemia (ATL) cells expressing Tax protein and forced expression of Pin1 in turn increases the Tax protein expression.
Identification of a novel motif responsible for the distinctive transforming activity of human T-cell leukemia virus (HTLV) type 1 Tax1 protein from HTLV-2 Tax2.
The pathogenic potential of human T-cell leukemia virus type 1 (HTLV-1) Tax protein is partly ascribed to its capacity to constitutively activate NF-kappaB factors because constitutive activity of these factors play an important role in the pathophysiology of adult T-cell leukemia (ATL) and tropical spastic paraparesis-HTLV-1 associated myelopathy (TSP-HAM).
The premature stop codon in tax gene existed in many non-ATL HTLV-I carriers as a minor population but not in the commonest HTLV-I sequence of the individual.
However, tax gene expression in ATL cells is disrupted by several mechanisms, including genetic changes in the tax gene and DNA methylation/deletion of the 5' long terminal repeat (LTR).
These findings indicate that Tax-targeted vaccines may be effective for prophylaxis of ATL in a high-risk group, and also for therapy of ATL in at least half the cases.
In ATL cases with genetic changes that could not produce Tax protein, the tax gene was frequently transcribed, suggesting that such cells do not need the transcriptional silencing.
Since the development of both TSP/HAM and ATL seems to depend on the viral Tax protein, we describe a possible system for anti Tax gene-therapy approach based on a negative transdominant mutant Tax gene.