scholarly journals Effect of Teriflunomide on Cells From Patients With Human T-cell Lymphotropic Virus Type 1–Associated Neurologic Disease

2021 ◽  
Vol 8 (3) ◽  
pp. e986
Author(s):  
Yoshimi Enose-Akahata ◽  
Nyater Ngouth ◽  
Joan Ohayon ◽  
Matt Mandel ◽  
Jeffrey Chavin ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Expression ◽  
Cell Viability ◽  
Virus Type ◽  
T Cell Subsets ◽  
Activation Markers ◽  
Tax Protein ◽  
Human T Cell ◽  
Spontaneous Proliferation

ObjectiveTo test the hypothesis that teriflunomide can reduce ex vivo spontaneous proliferation of peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP).MethodsPBMCs from patients with HAM/TSP were cultured in the presence and absence of teriflunomide and assessed for cell viability, lymphocyte proliferation, activation markers, HTLV-1 tax and HTLV-1 hbz messenger ribonucleic acid (mRNA) expression, and HTLV-1 Tax protein expression.ResultsIn culture, teriflunomide did not affect cell viability. A concentration-dependent reduction in spontaneous proliferation of PBMCs was observed with 25 μM (38.3% inhibition), 50 μM (65.8% inhibition), and 100 μM (90.7% inhibition) teriflunomide. The inhibitory effects of teriflunomide were detected in both CD8+ and CD4+ T-cell subsets, which are involved in the immune response to HTLV-1 infection and the pathogenesis of HAM/TSP. There was no significant change in HTLV-1 proviral load (PVL) or tax mRNA/Tax protein expression in these short-term cultures, but there was a significant reduction of HTLV-1 PVL due to inhibition of proliferation of CD4+ T cells obtained from a subset of patients with HAM/TSP.ConclusionsThese results suggest that teriflunomide inhibits abnormal T-cell proliferation associated with HTLV-1 infection and may have potential as a therapeutic option in patients with HAM/TSP.

scholarly journals Cloning of Novel Isoforms of the Human Gli2 Oncogene and Their Activities To Enhance Tax-Dependent Transcription of the Human T-Cell Leukemia Virus Type 1 Genome

1998 ◽  
Vol 72 (5) ◽  
pp. 3958-3964 ◽  
Author(s):  
Akira Tanimura ◽  
Shingo Dan ◽  
Mitsuaki Yoshida
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Virus Type ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Tax Protein ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT The expression of human T-cell leukemia virus type 1 (HTLV-1) is activated by interaction of a viral transactivator protein, Tax, and cellular transcription factor, CREB (cyclic AMP response element binding protein), which bind to a 21-bp enhancer in the long terminal repeats (LTR). THP (Tax-helping protein) was previously determined to enhance the transactivation by Tax protein. Here we report novel forms of the human homolog of a member of the Gli oncogene family, Gli2 (also termed Gli2/THP), an extended form of a zinc finger protein, THP, which was described previously. Four possible isoforms (hGli2 α, β, γ, and δ) are formed by combinations of two independent alternative splicings, and all the isoforms could bind to a DNA motif, TRE2S, in the LTR. The longer isoforms, α and β, were abundantly expressed in various cell lines including HTLV-1-infected T-cell lines. Fusion proteins of the hGli2 isoforms with the DNA-binding domain of Gal4 activated transcription when the reporter contained a Gal4-binding site and one copy of the 21-bp sequence, to which CREB binds. This activation was observed only in the presence of Tax. The 21-bp sequence in the reporter was also essential for the activation. These results suggest that simultaneous binding of hGli2 and CREB to the respective sites in the reporter seems to be critical for Tax protein to activate transcription. Consequently, it is probable that the LTR can be regulated by two independent signals through hGli2 and CREB, since the LTR contains the 21-bp and TRE2S sequences in the vicinity.

scholarly journals Human T-Cell Leukemia Virus Type 1 Tax Protein Induces the Expression of Lymphocyte Chemoattractant SDF-1/PBSF

Virology ◽  
1998 ◽  
Vol 241 (2) ◽  
pp. 298-303 ◽  
Author(s):  
Masaaki Arai ◽  
Takashi Ohashi ◽  
Tomonori Tsukahara ◽  
Tsutomu Murakami ◽  
Toshiyuki Hori ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Tax Protein ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Transactivation of human osteopontin promoter by human T-cell leukemia virus type 1-encoded Tax protein

2010 ◽  
Vol 34 (6) ◽  
pp. 763-768 ◽  
Author(s):  
Jing Zhang ◽  
Osamu Yamada ◽  
Yoshihisa Matsushita ◽  
Haorile Chagan-Yasutan ◽  
Toshio Hattori
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Tax Protein ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Identification of CD44 as a downstream target of noncanonical NF-κB pathway activated by Human T-cell leukemia virus type 1-encoded Tax protein

Virology ◽  
2011 ◽  
Vol 413 (2) ◽  
pp. 244-252 ◽  
Author(s):  
Jing Zhang ◽  
Osamu Yamada ◽  
Shinya Kida ◽  
Yoshihisa Matsushita ◽  
Shoji Yamaoka ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Downstream Target ◽  
Tax Protein ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals The Human T-cell Leukemia Virus Type-1 Tax Protein Regulates the Activity of the IκB Kinase Complex

1999 ◽  
Vol 274 (48) ◽  
pp. 34417-34424 ◽  
Author(s):  
Xiao Hua Li ◽  
Kathleen M. Murphy ◽  
Kevin T. Palka ◽  
Rama Mohan Surabhi ◽  
Richard B. Gaynor
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Tax Protein ◽  
Iκb Kinase ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Upregulation of Human T-Cell Leukemia Virus Type 1 Antisense Transcription by the Viral Tax Protein

2008 ◽  
Vol 83 (4) ◽  
pp. 2048-2054 ◽  
Author(s):  
Sébastien Landry ◽  
Marilène Halin ◽  
Amandine Vargas ◽  
Isabelle Lemasson ◽  
Jean-Michel Mesnard ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Antisense Transcription ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Tax Protein ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT Several studies have recently demonstrated the existence of human T-cell leukemia virus type 1 (HTLV-1) antisense transcripts, which allow the synthesis of the newly described HBZ protein. Although previous reports have been aimed at understanding the potential role of the HBZ protein in HTLV-1 pathogenesis, little is known as to how this viral gene is regulated. Here, using our K30-3′asLuc reporter construct, we show that the viral Tax protein upregulates antisense transcription through its action on the TRE sequences located in the 3′ long terminal repeat. Generation of stable clones in 293T cells demonstrated that Tax-induced HBZ expression is importantly influenced by the integration site in the host genome. The cellular DNA context could thus affect the level of HBZ mRNA expression in infected cells.

scholarly journals Distinct p300-Responsive Mechanisms Promote Caspase-Dependent Apoptosis by Human T-Cell Lymphotropic Virus Type 1 Tax Protein

2000 ◽  
Vol 20 (22) ◽  
pp. 8580-8589 ◽  
Author(s):  
Christophe Nicot ◽  
Robert Harrod
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Virus Type ◽  
Ectopic Expression ◽  
Early Event ◽  
Nuclear Expression ◽  
Tax Protein ◽  
Human T Cell ◽  
P300 Binding

ABSTRACT The dysregulation of cellular apoptosis pathways has emerged as a critical early event associated with the development of many types of human cancers. Numerous viral and cellular oncogenes, aside from their inherent transforming properties, are known to induce programmed cell death, consistent with the hypothesis that genetic defects are required to support tumor survival. Here, we report that nuclear expression of the CREB-binding protein (CBP)/p300-binding domain of the human T-cell lymphotropic virus type 1 (HTLV-1) transactivator, Tax, triggers an apoptotic death-inducing signal during short-term clonal analyses, as well as in transient cell death assays. Coexpression of the antiapoptotic factor Bcl-2 increased serum stimulation; incubation with the chemical caspase inhibitor z-Val-Ala-dl-Asp fluoromethylketone antagonized Tax-induced cell death. The CBP/p300-binding defective Tax mutants K88A and V89A exhibited markedly reduced cytotoxic effects compared to the wild-type Tax protein. Importantly, nuclear expression of the minimal CBP/p300-binding peptide of Tax induced apoptosis in the absence of Tax-dependent transcriptional activities, while its K88A counterpart did not cause cell death. Further, Tax-mediated apoptosis was effectively prevented by ectopic expression of the p300 coactivator. We also report that activation of the NF-κB transcription pathway by Tax, under growth arrest conditions, results in apoptosis that occurs independent of direct Tax coactivator effects. Our results allude to a novel pivotal role for the transcriptional coactivator p300 in determining cell fate and raise the possibility that dysregulated coactivator usage may pose an early barrier to transformation that must be selectively overcome as a prerequisite for the initiation of neoplasia.

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