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

Matsuda, Takehiro; Almasan, Alexandru; Tomita, Masaru; Uchihara, Jun Nosuke; Masuda, Masato; Ohshiro, Kazuiku; Takasu, Nobuyuki; Yagita, Hideo; Ohta, Takao; Mori, Nozomu

doi:10.1128/jvi.79.3.1367-1378.2005

Cited by 23 publications

(8 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We were interested in the activity of the M22 Tax mutant since Tax transactivates survival genes including Bcl-xL by NF-kB activation, thereby protecting cells from apoptosis induced by other agents such as IL-2 or Apo-2 (Tsukahara et al, 1999;Matsuda et al, 2005). To investigate whether Tax could attenuate p53-independent apoptosis through its transcriptional activities, HCT-116 p53 knockout cells transiently expressing wild-type or mutant Tax proteins were irradiated and fixed with 1% formaldehyde and 70% ethanol 24 h Tax/Chk2 interaction attenuates the DNA-damage-induced apoptosis HU Park et al post-g-IR followed by TUNEL assay.…”

Section: Resultsmentioning

confidence: 99%

“…These findings support that Chk2 does not regulate G 2 accumulation but apoptosis in response to DNA damage. Recent studies have shown that HTLV-1 Tax protects cells from apoptosis induced by activation of cell surface markers such as IL-2 or Apo-2 receptors (Tsukahara et al, 1999;Matsuda et al, 2005). Protection is dependent upon the ability of Tax to activate the NF-kB pathway.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Human T-cell leukemia virus type 1 Tax attenuates γ-irradiation-induced apoptosis through physical interaction with Chk2

Jeong

et al. 2005

Oncogene

View full text Add to dashboard Cite

Checkpoint kinase 2 (Chk2) is known to mediate diverse cellular responses to genotoxic stress. The fundamental role of Chk2 is to regulate the network of genomesurveillance pathways that coordinate cell-cycle progression with DNA repair and cell survival or death. Defects in Chk2 contribute to the development of both hereditary and sporadic human cancers. We now present evidence that the human T-cell leukemia virus type-1 (HTLV-1) Tax protein directly interacts with Chk2 and the kinase activity of Chk2 is inhibited by Tax. The physical interaction of Chk2 and Tax was observed by coimmunoprecipitation assays in HTLV-1-infected T cells (C81) as well as GST pull-down assays using purified proteins. Binding and kinase activity inhibition studies with Tax deletion mutants indicated that at least two domains of Tax mediate the interaction with Chk2. We have analysed the functional consequence of de novo expression of Tax upon the cellular DNA-damage-induced apoptosis, which is mediated by Chk2. Using transient transfection and TUNEL assay, we found that cirradiation-induced apoptosis was decreased in 293T and HCT-116 (p53 À/À ) cells expressing HTLV-1 Tax. Our studies demonstrate an important potential target of Tax in cellular transformation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human T-cell leukemia virus type 1 Tax attenuates γ-irradiation-induced apoptosis through physical interaction with Chk2

Jeong

et al. 2005

Oncogene

View full text Add to dashboard Cite

show abstract

“…In particular, Kaposi sarcomaassociated human herpesvirus 8 and related gammaherpesviruses prevent the triggering of TRAIL-induced apoptosis by encoding viral FLICE-inhibitory proteins (vFLIPs) that interact with the Fas-associated death domain (FADD) to inhibit active caspase 8 generation (34). Additionally, T cells infected with human-T cell leukemia virus type 1 are resistant to TRAIL-mediated apoptosis by the viral transactivator Tax (35). Furthermore, three proteins (E3 RID) encoded by the human adenovirus type 5 induce the internalization of TRAIL receptors from the cell surface targeting lysosomal degradation (36).…”

Section: Discussionmentioning

confidence: 99%

Nef Is Dispensable for Resistance of Simian Immunodeficiency Virus-Infected Macrophages to CD8 ⁺ T Cell Killing

Rainho

Martins

Cunyat

et al. 2015

J Virol

View full text Add to dashboard Cite

Simian immunodeficiency virus (SIV)-specific CD8؉ T cells kill SIV-infected CD4 ؉ T cells in an major histocompatibility complex class I (MHC-I)-dependent manner. However, they are reportedly less efficient at killing SIV-infected macrophages. Since the viral accessory protein Nef has been shown to downregulate MHC-I molecules and enhance cytotoxic T lymphocyte (CTL) evasion in human immunodeficiency virus type 1 (HIV-1)-infected CD4؉ T cells, we examined whether Nef played a role in protecting SIV-infected macrophages from killing by SIV-specific CD8 ؉ T cells. To explore the role of Nef in CD8 ؉ T cell evasion, we compared the ability of freshly sorted SIV-specific CD8 ؉ T cells to readily suppress viral replication or eliminate CD4 ؉ T cells or monocyte-derived macrophages infected with SIV variants containing wild-type (WT) or mutated nef genes. As expected, SIVspecific CD8؉ T cells suppressed viral replication and eliminated the majority of SIV-infected CD4 ؉ T cells, and this killing was enhanced in CD4؉ T cells infected with the nef variants. However, macrophages infected with nef variants that disrupt MHC-I downregulation did not promote rapid killing by freshly isolated CD8 ؉ T cells. These results suggest that mechanisms other than Nef-mediated MHC-I downregulation govern the resistance of SIV-infected macrophages to CD8؉ T cell-mediated killing. This study has implications for viral persistence and suggests that macrophages may afford primate lentiviruses some degree of protection from immune surveillance. Macrophages may play an important role in human immunodeficiency virus type 1/simian immunodeficiency virus (HIV-1/SIV) pathogenesis. Infection of microglia and perivascular macrophages actively mediates entry of HIV-1 into the central nervous system (CNS), resulting in HIV-associated dementia, encephalitis, cognitive disorder, and peripheral neuropathy (1). Accumulating data suggest that tissue macrophages are an important reservoir of virus. Infection of rhesus macaques with a highly pathogenic hybrid simian-human immunodeficiency virus (SHIV) resulted in the rapid depletion of CD4 ϩ T cells such that macrophages were the principal reservoir that sustained high viral loads in the SHIV-infected animals (2). In another study, rhesus macaques depleted of CD4 ϩ T cells exhibited higher viral loads than nondepleted animals, and in situ staining performed on gut tissue revealed that macrophages were the primary source of viral replication (3). It has also been suggested that the level of monocyte turnover is responsible for disease progression in the macaque model of AIDS (4).Macrophages present unique obstacles to infection by primate lentiviruses. The nondividing status of terminally differentiated macrophages and low deoxynucleoside triphosphate (dNTP) levels have to be accommodated in order for primate lentiviruses to establish a productive infection (5, 6). Additionally, macrophages are resistant to the cytopathic effects of viral replication in comparison to the sensitivity of activated ...

show abstract

“…NFκB also upregulates FasL and together, these proapoptotic ligands may be responsible for tumor-cell elimination in immune surveillance and/or attenuation of T-cell activation to prevent autoimmunity. NFκB is also responsible for constitutive TRAIL expression in human T-cell leukemia virus type I (HTLV-1)-induced leukemia, though other concomitant effects of NFκB seem to cause resistance to TRAIL-mediated apoptosis 64 . In accordance with a positive regulatory role for NFκB with respect to the TRAIL gene, the prostaglandin 15d-PGJ2 represses TRAIL gene transcription by inhibiting the binding of NFκB to the NFκB binding site 1 (Fig.…”

Section: Regulation Of the Human Trail Genementioning

confidence: 99%

Regulation of the human TRAIL gene

Allen

El‐Deiry

2012

Cancer Biology & Therapy

View full text Add to dashboard Cite

TRAIL is a member of the TNF superfamily that induces tumor-selective cell death by engaging the pro-apoptotic death receptors DR4 and DR5. The antitumor potential of the TRAIL pathway has been targeted by several therapeutic approaches including recombinant TRAIL and TRAIL-receptor agonist antibodies among others. Interest in sensitizing tumor cells to TRAIL-mediated apoptosis has driven investigations of TRAIL-receptor gene regulation, though regulation of the TRAIL gene has been less studied. Physiologically, TRAIL serves as a pro-apoptotic effector molecule in the immune surveillance of cancer that is conditionally expressed by immune cells upon stimulation via an interferon-response element that was identified in early studies of the TRAIL gene promoter. Here, we map the TRAIL gene promoter and review studies of TRAIL gene regulation that involve several modalities of gene regulation including transcription factors, epigenetics, single-nucleotide polymorphisms and functionally distinct isoforms.

show abstract

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

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-

Cited by 23 publications

References 67 publications

Human T-cell leukemia virus type 1 Tax attenuates γ-irradiation-induced apoptosis through physical interaction with Chk2

Human T-cell leukemia virus type 1 Tax attenuates γ-irradiation-induced apoptosis through physical interaction with Chk2

Nef Is Dispensable for Resistance of Simian Immunodeficiency Virus-Infected Macrophages to CD8 ⁺ T Cell Killing

Regulation of the human TRAIL gene

Contact Info

Product

Resources

About

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

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-

Cited by 23 publications

References 67 publications

Human T-cell leukemia virus type 1 Tax attenuates γ-irradiation-induced apoptosis through physical interaction with Chk2

Human T-cell leukemia virus type 1 Tax attenuates γ-irradiation-induced apoptosis through physical interaction with Chk2

Nef Is Dispensable for Resistance of Simian Immunodeficiency Virus-Infected Macrophages to CD8 + T Cell Killing

Regulation of the human TRAIL gene

Contact Info

Product

Resources

About

Nef Is Dispensable for Resistance of Simian Immunodeficiency Virus-Infected Macrophages to CD8 ⁺ T Cell Killing