scholarly journals Important Roles of Cellular MicroRNA miR-155 in Leukemogenesis by Human T-Cell Leukemia Virus Type 1 Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Mariko Tomita
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
T Cell Lines

Human T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes the aggressive and lethal malignancy of CD4+ T-lymphocytes called adult T-cell leukemia/lymphoma (ATLL). MicroRNAs (miRNAs), a class of short, noncoding RNAs, regulate gene expression by targeting mRNAs for translational repression or cleavage. miRNAs are involved in many aspects of cell biology linked with formation of several cancer phenotypes. However, the relation between miRNAs and pathologic implication in ATLL is not well elucidated. Here, we evaluated the roles of cellular miRNAs in ATLL caused by HTLV-1. We found that the expression of miR-155 was increased in HTLV-1-positive T-cell lines. miR-155 expression was enhanced by Tax and binding of transcription factors, NF-κB and AP-1, on the transcription binding sites of miR-155 gene promoter region is important to increase the expression of miR-155 by Tax. Transfection of anti-miR-155 inhibitor, which inhibits the function of miR-155, inhibited the growth of HTLV-1-positive T-cell lines. On the other hand, the growth of HTLV-1-negative T-cell lines was not changed by transfection of anti-miR-155. Forced expression of miR-155 enhanced the growth of HTLV-1-positive T-cell lines. These findings indicate that targeting the functions of miRNAs is a novel approach to the prevention or treatment of ATLL.

scholarly journals Resistance to Apo2 Ligand (Apo2L)/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Mediated Apoptosis and Constitutive Expression of Apo2L/TRAIL in Human T-Cell Leukemia Virus Type 1-Infected T-Cell Lines

2005 ◽  
Vol 79 (3) ◽  
pp. 1367-1378 ◽  
Author(s):  
Takehiro Matsuda ◽  
Alex Almasan ◽  
Mariko Tomita ◽  
Jun-nosuke Uchihara ◽  
Masato Masuda ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Induced Apoptosis ◽  
T Cell Lines

ABSTRACT Adult T-cell leukemia (ATL), a CD4+-T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1), is difficult to cure, and novel treatments are urgently needed. Apo2 ligand (Apo2L; also tumor necrosis factor-related apoptosis-inducing ligand [TRAIL]) has been implicated in antitumor therapy. We found that HTLV-1-infected T-cell lines and primary ATL cells were more resistant to Apo2L-induced apoptosis than uninfected cells. Interestingly, HTLV-1-infected T-cell lines and primary ATL cells constitutively expressed Apo2L mRNA. Inducible expression of the viral oncoprotein Tax in a T-cell line up-regulated Apo2L mRNA. Analysis of the Apo2L promoter revealed that this gene is activated by Tax via the activation of NF-κB. The sensitivity to Apo2L was not correlated with expression levels of Apo2L receptors, intracellular regulators of apoptosis (FLICE-inhibitory protein and active Akt). NF-κB plays a crucial role in the pathogenesis and survival of ATL cells. The resistance to Apo2L-induced apoptosis was reversed by N-acetyl-l-leucinyl-l-leucinyl-l-norleucinal (LLnL), an NF-κB inhibitor. LLnL significantly induced the Apo2L receptors DR4 and DR5. Our results suggest that the constitutive activation of NF-κB is essential for Apo2L gene induction and protection against Apo2L-induced apoptosis and that suppression of NF-κB may be a useful adjunct in clinical use of Apo2L against ATL.

scholarly journals Tocilizumab has no direct effect on cell lines infected with human T-cell leukemia virus type 1

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052110020
Author(s):  
Yushiro Endo ◽  
Shoichi Fukui ◽  
Tomohiro Koga ◽  
Daisuke Sasaki ◽  
Hiroo Hasegawa ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
T Cell Lines

Objective It remains unclear whether human T-cell leukemia virus type 1 (HTLV-1) infection influences therapeutic responses in patients with rheumatic diseases and whether immunosuppressive treatments increase the risk of HTLV-1-related complications in HTLV-1 carriers with rheumatic diseases. We examined the effects of tocilizumab (TCZ), an interleukin (IL)-6 receptor antagonist, on two HTLV-1-infected T-cell lines (HCT-5 and MT-2) in vitro. Methods We evaluated production of cytokines and chemokines, expression of HTLV-I associated genes, HTLV-1 proviral load (PVL), expression of HTLV-1 structural proteins, and apoptosis. Results There were no significant differences in cytokine and chemokine levels in the culture supernatants of HCT-5 and MT-2 cells treated with phosphate-buffered saline (PBS) or TCZ. No significant differences were detected in mRNA abundance of Tax or HBZ, PVL, expression of the HTLV-1 structural protein GAG, or apoptosis among HCT-5 and MT-2 cells treated with PBS or TCZ. Conclusions TCZ had no effect the cytokine profiles, HTLV-1 gene and protein expression, PVL, or apoptosis in HTLV-1-infected T-cell lines. Thus, TCZ treatment has no effect on HTLV-1 infection in vitro.

scholarly journals Smoking is a risk factor for development of adult T-cell leukemia/lymphoma in Japanese human T-cell leukemia virus type-1 carriers

2016 ◽  
Vol 27 (9) ◽  
pp. 1059-1066 ◽  
Author(s):  
Hisayoshi Kondo ◽  
Midori Soda ◽  
Norie Sawada ◽  
Manami Inoue ◽  
Yoshitaka Imaizumi ◽  
...  
Keyword(s):  
Risk Factor ◽  
T Cell ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with Indeterminate Western Blot Analysis Results

2017 ◽  
Vol 55 (9) ◽  
pp. 2838-2849 ◽  
Author(s):  
Madoka Kuramitsu ◽  
Tsuyoshi Sekizuka ◽  
Tadanori Yamochi ◽  
Sanaz Firouzi ◽  
Tomoo Sato ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Proviral Load ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACTWestern blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of the complete HTLV-1 genomes of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions, composed of four types, G to A (29%), C to T (19%), T to C (19%), and A to G (16%). In the most frequent G-to-A substitution, 64% occurred at GG dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB-indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings suggest that WB-indeterminate carriers have low production of viral antigens because of a combination of a low proviral load and mutations in the provirus, which may interfere with host recognition of HTLV-1 antigens.

scholarly journals Human T Cell Leukemia Virus Type 1 Tax Inhibits Innate Antiviral Signaling via NF- B-Dependent Induction of SOCS1

2011 ◽  
Vol 85 (14) ◽  
pp. 6955-6962 ◽  
Author(s):  
S. Charoenthongtrakul ◽  
Q. Zhou ◽  
N. Shembade ◽  
N. S. Harhaj ◽  
E. W. Harhaj
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Antiviral Signaling ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Functional Comparison of HBZ and the Related APH-2 Protein Provides Insight into Human T-Cell Leukemia Virus Type 1 Pathogenesis

2016 ◽  
Vol 90 (7) ◽  
pp. 3760-3772 ◽  
Author(s):  
Amanda R. Panfil ◽  
Nathan J. Dissinger ◽  
Cory M. Howard ◽  
Brandon M. Murphy ◽  
Kristina Landes ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Antisense Strand ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACTHuman T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are highly related retroviruses that transform T cellsin vitrobut have distinct pathological outcomesin vivo. HTLV-1 encodes a protein from the antisense strand of its proviral genome, the HTLV-1 basic leucine zipper factor (HBZ), which inhibits Tax-1-mediated viral transcription and promotes cell proliferation, a high proviral load, and persistencein vivo. In adult T-cell leukemia/lymphoma (ATL) cell lines and patient T cells,hbzis often the only viral gene expressed. The antisense strand of the HTLV-2 proviral genome also encodes a protein termed APH-2. Like HBZ, APH-2 is able to inhibit Tax-2-mediated viral transcription and is detectable in most primary lymphocytes from HTLV-2-infected patients. However, unlike HBZ, the loss of APH-2in vivoresults in increased viral replication and proviral loads, suggesting that HBZ and APH-2 modulate the virus and cellular pathways differently. Herein, we examined the effect of APH-2 on several known HBZ-modulated pathways: NF-κB (p65) transactivation, transforming growth factor β (TGF-β) signaling, and interferon regulatory factor 1 (IRF-1) transactivation. Like HBZ, APH-2 has the ability to inhibit p65 transactivation. Conversely, HBZ and APH-2 have divergent effects on TGF-β signaling and IRF-1 transactivation. Quantitative PCR and protein half-life experiments revealed a substantial disparity between HBZ and APH-2 transcript levels and protein stability, respectively. Taken together, our data further elucidate the functional differences between HBZ and APH-2 and how these differences can have profound effects on the survival of infected cells and, ultimately, pathogenesis.IMPORTANCEHuman T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are highly related retroviruses that have distinct pathological outcomes in infected hosts. Functional comparisons of HTLV-1 and HTLV-2 proteins provide a better understanding about how HTLV-1 infection is associated with disease and HTLV-2 infection is not. The HTLV genome antisense-strand geneshbzandaph-2are often the only viral genes expressed in HTLV-infected T cells. Previously, our group found that HTLV-1 HBZ and HTLV-2 APH-2 had distinct effectsin vivoand hypothesized that the differences in the interactions of HBZ and APH-2 with important cell signaling pathways dictate whether cells undergo proliferation, apoptosis, or senescence. Ultimately, these functional differences may affect how HTLV-1 causes disease but HTLV-2 generally does not. In the current study, we compared the effects of HBZ and APH-2 on several HTLV-relevant cellular pathways, including the TGF-β signaling, NF-κB activation, and IRF-1 transactivation pathways.

scholarly journals CD69 overexpression by human T-cell leukemia virus type 1 Tax transactivation

2013 ◽  
Vol 1833 (6) ◽  
pp. 1542-1552 ◽  
Author(s):  
Chie Ishikawa ◽  
Hirochika Kawakami ◽  
Jun-Nosuke Uchihara ◽  
Masachika Senba ◽  
Naoki Mori
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus
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