Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-κB

Zhao, Tiejun; Yasunaga, Jun-ichirou; Satou, Yorifumi; Nakao, Mitsuyoshi; Takahashi, Masahiko; Fujii, Masahiro; Matsuoka, Masao

doi:10.1182/blood-2008-06-161729

Cited by 158 publications

(198 citation statements)

References 57 publications

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“…Valproate acts on class I and II histone deacetylases, which collectively deacetylate a variety of nuclear and cytoplasmic proteins, so its effects are inevitably pleiotropic. For example, valproate induces oxidative stress, with increased levels of reactive oxygen species; thus, antioxidants can improve some of its side effects [18,19]. Our previous studies (Boostani et al, unpublished data), and a recent Japanese study [49], showed that the prescription of antioxidant agents had positive or improving effects on signs and symptoms of HAM/TSP.…”

Section: Discussionmentioning

confidence: 99%

“…HBZ expression has a positive effect on HTLV-1 viral replication [17]. Moreover, a significant positive correlation has been previously reported between HBZ mRNA expression and HAM/TSP disease severity [18][19][20]. HTLV-1-infected cells circulate in the body; hence, blood samples provide an easily accessible source of information and, in particular, a large number of viruses for the understanding and monitoring of HTLV-1-associated diseases.…”

Section: Introductionmentioning

confidence: 99%

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Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

et al. 2015

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Considering that there is no effective treatment for human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis, this study aimed to assess the impact of triple combination therapy-interferon-α, valproic acid, and prednisolone-on clinical outcomes, main HTLV-1 viral factors, and host anti-HTLV-1 antibody response. HTLV-1 proviral load (PVL), and HBZ and Tax mRNA expression levels were measured in peripheral blood mononuclear cells of 13 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis before and after treatment with 180 μg pegylated interferon once a week, 10-20 mg/kg/day sodium valproate, and 5 mg/day prednisolone for 25 weeks using a TaqMan real-time polymerase chain reaction assay. Furthermore, anti-HTLV-1 titer, Osame Motor Disability Score, Ashworth spasticity scale, and urinary symptoms (through standard questionnaire and clinical monitoring) were assessed in patients before and after the treatment. HTLV-1 PVL and HBZ expression significantly decreased after the treatment [PVL from 1443±282 to 660±137 copies/10 4 peripheral blood mononuclear cells (p= 0.01); and HBZ from 8.0±1.5 to 3.0±0.66 (p<0.01)]. Tax mRNA expression decreased after the treatment from 2.26± 0.45 to 1.44±0.64, but this reduction was not statistically significant (p=0.10). Furthermore, anti-HTLV-1 titer reduced dramatically after the treatment, from 3123±395 to 815±239 (p<0.01). Clinical signs and symptoms, according to Osame Motor Disability Score and Ashworth score, improved significantly (both p<0.01). Urinary symptoms and sensory disturbances with lower back pain were reduced, though not to a statistically significant degree. Although signs and symptoms of spasticity were improved, frequent urination and urinary incontinence were not significantly affected by the triple therapy. The results provide new insight into the complicated conditions underlying HTLV-1-associated diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

et al. 2015

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“…This study shows that TCF1/LEF1 inhibit Taxmediated NF-κB activation by direct binding to Tax. Furthermore, TCF1/LEF1 inhibit various functions of Tax, whereas HBZ selectively modulates signaling pathways (43,44). Thus, Tax and HBZ collaboratively function for clonal expansion and viral replication, whereas TCF1/LEF1 inhibit functions of Tax by direct interaction, which leads to suppression of viral replication and proliferation of infected cells.…”

Section: Discussionmentioning

confidence: 99%

TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax

Ma¹,

Yasunaga²,

Akari³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…HBZ et Tax ont globalement des effets opposés sur la plupart des voies de signalisation [64]. Tax active en particulier les voies canonique et non canonique de la signalisation NF B alors que HBZ inactive la voie canonique en induisant la dégra-dation de la sous-unité p65 de NF B par le protéasome [65]. Enfin, les souris transgéniques HBZ [61,66] …”

Section: Mutations Ponctuelles Et Anomalies éPigénétiquesunclassified