The Experts below are selected from a list of 21 Experts worldwide ranked by ideXlab platform
Alexander Y. Tsygankov - One of the best experts on this subject based on the ideXlab platform.
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Cell transformation by Herpesvirus saimiri.
Journal of Cellular Physiology, 2005Co-Authors: Alexander Y. TsygankovAbstract:Herpesvirus saimiri (Saimiriine Herpesvirus-2), a γ2-Herpesvirus (rhadinovirus) of non-human primates, causes T-lymphoproliferative diseases in susceptible organisms and transforms human and non-human T lymphocytes to continuous growth in vitro in the absence of stimulation. T cells transformed by H. saimiri retain many characteristics of intact T lymphocytes, such as the sensitivity to interleukin-2 and the ability to recognize the corresponding antigens. As a result, H. saimiri is widely used in immunobiology for immortalization of various difficult-to-obtain and/or -to-maintain T cells in order to obtain useful experimental models. In particular, H. saimiri-transformed human T cells are highly susceptible to infection with HIV-1 and -2. This makes them a convenient tool for propagation of poorly replicating strains of HIV, including primary clinical isolates. Therefore, the mechanisms mediating transformation of T cells by H. saimiri are of considerable interest. A single transformation-associated protein, StpA or StpB, mediates cell transformation by H. saimiri strains of group A or B, respectively. Strains of group C, which exhibit the highest oncogenic potential, have two proteins involved in transformation—StpC and Tip. Both proteins have been shown to dramatically affect signal transduction pathways leading to the activation of crucial transcription factors. This review is focused on the biological effects and molecular mechanisms of action of proteins involved in H. saimiri-dependent transformation. © 2004 Wiley-Liss, Inc.
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Tip, an Lck-interacting protein of Herpesvirus saimiri, causes Fas- and Lck-dependent apoptosis of T lymphocytes
Virology, 2004Co-Authors: Muneer G. Hasham, Alexander Y. TsygankovAbstract:Saimiriine Herpesvirus-2 (Herpesvirus saimiri) transforms T lymphocytes, including human, to continuous growth in vitro. H. saimiri-induced transformation is becoming an important tool of T-cell biology, including studies of HIV replication. Two proteins of H. saimiri subgroup C, Tip and StpC, are essential for T-cell transformation. In spite of the important role of these proteins, their biological functions and the molecular mechanisms of their action remain insufficiently understood. To further elucidate the effects of Tip on T cells, we transduced T lymphocytes, using an efficient lentiviral gene transfer system, to express Tip in the absence of other H. saimiri proteins. Our results indicate that Tip specifically inhibits IL-2 production by human T lymphocytes. Furthermore, Tip promotes T-cell apoptosis, which appears to be the reason for the observed decrease in IL-2 production. Finally, the apoptotic effect of Tip in T cells is mediated by Fas and requires the presence of active Lck in the cell.
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Molecular mechanisms of the effect of Herpesvirus saimiri protein StpC on the signaling pathway leading to NF-κB activation
Journal of Biological Chemistry, 2004Co-Authors: Elena M. Sorokina, Joseph J. Merlo, Alexander Y. TsygankovAbstract:Abstract Herpesvirus saimiri (Saimiriine Herpesvirus-2) causes lethal T lymphoproliferative diseases in the susceptible species and transforms T lymphocytes to continuous growth in vitro. H. saimiri-induced transformation of T cells is becoming an important experimental tool of biomedical research. Two proteins of H. saimiri subgroup C, Tip and StpC, are essential for T cell transformation by this virus. It has been shown previously that StpC transforms fibroblasts, activates NF-κB, and binds to tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins, but the molecular mechanism of its action remains insufficiently understood. This study further characterized the effect of StpC on NF-κB. First, StpC activates NF-κB via the consensus pathway involving activation of I-κB kinase and subsequent phosphorylation and degradation of I-κB in both T lymphoid and epithelial cells. Second, triggering of this pathway by StpC in both T lymphoid and epithelial cells is dependent on the presence of functional NF-κB-inducing kinase (NIK). Third, StpC physically interacts with TRAF in epithelial cells, and the effect of StpC on NF-κB activity in these cells requires the presence of functional TRAF. Finally the effect of StpC is completely independent of TNF-α, a well described stimulus of NF-κB activity. Moreover it appears that StpC uncouples stimulation of NF-κB activity from TNF-α stimulation. Overall these results argue that the effect of StpC on NF-κB is similar to the effects of other viral proteins, “usurping” the TRAF/NIK/I-κB kinase pathway, and reinforce the notion that the role of StpC in cell transformation by H. saimiri may be mediated by signaling that results in NF-κB activation.
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Herpesvirus saimiri Oncoproteins Tip and StpC Synergistically Stimulate NF-κB Activity and Interleukin-2 Gene Expression
Virology, 2001Co-Authors: Joseph J. Merlo, Alexander Y. TsygankovAbstract:Abstract Saimiriine Herpesvirus 2 (Herpesvirus saimiri) is capable of inducing lethal T-cell lymphoproliferative diseases in primates and of immortalizing human T lymphocytes in vitro. Two viral oncoproteins, Tip and StpC, are essential for T-cell transformation by Herpesvirus saimiri strains of the subgroup C, which exhibits a higher transformation potential than other subgroups of this virus. Despite the importance of these proteins, the molecular basis of their effects on T cells is poorly understood. It remains unclear how Tip and StpC affect gene expression and what is the molecular basis of their cooperation. To address these issues, we expressed Tip and StpC in T lymphoblastoid cells and assessed both their effects on and transcription factors involved in IL-2 gene expression. Our study shows that Tip and StpC cooperate to upregulate IL-2 gene expression, that their effect is mediated primarily by NF-κB and NF-AT, which is partially dependent on tyrosine phosphorylation.
Joseph J. Merlo - One of the best experts on this subject based on the ideXlab platform.
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Molecular mechanisms of the effect of Herpesvirus saimiri protein StpC on the signaling pathway leading to NF-κB activation
Journal of Biological Chemistry, 2004Co-Authors: Elena M. Sorokina, Joseph J. Merlo, Alexander Y. TsygankovAbstract:Abstract Herpesvirus saimiri (Saimiriine Herpesvirus-2) causes lethal T lymphoproliferative diseases in the susceptible species and transforms T lymphocytes to continuous growth in vitro. H. saimiri-induced transformation of T cells is becoming an important experimental tool of biomedical research. Two proteins of H. saimiri subgroup C, Tip and StpC, are essential for T cell transformation by this virus. It has been shown previously that StpC transforms fibroblasts, activates NF-κB, and binds to tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins, but the molecular mechanism of its action remains insufficiently understood. This study further characterized the effect of StpC on NF-κB. First, StpC activates NF-κB via the consensus pathway involving activation of I-κB kinase and subsequent phosphorylation and degradation of I-κB in both T lymphoid and epithelial cells. Second, triggering of this pathway by StpC in both T lymphoid and epithelial cells is dependent on the presence of functional NF-κB-inducing kinase (NIK). Third, StpC physically interacts with TRAF in epithelial cells, and the effect of StpC on NF-κB activity in these cells requires the presence of functional TRAF. Finally the effect of StpC is completely independent of TNF-α, a well described stimulus of NF-κB activity. Moreover it appears that StpC uncouples stimulation of NF-κB activity from TNF-α stimulation. Overall these results argue that the effect of StpC on NF-κB is similar to the effects of other viral proteins, “usurping” the TRAF/NIK/I-κB kinase pathway, and reinforce the notion that the role of StpC in cell transformation by H. saimiri may be mediated by signaling that results in NF-κB activation.
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Herpesvirus saimiri Oncoproteins Tip and StpC Synergistically Stimulate NF-κB Activity and Interleukin-2 Gene Expression
Virology, 2001Co-Authors: Joseph J. Merlo, Alexander Y. TsygankovAbstract:Abstract Saimiriine Herpesvirus 2 (Herpesvirus saimiri) is capable of inducing lethal T-cell lymphoproliferative diseases in primates and of immortalizing human T lymphocytes in vitro. Two viral oncoproteins, Tip and StpC, are essential for T-cell transformation by Herpesvirus saimiri strains of the subgroup C, which exhibits a higher transformation potential than other subgroups of this virus. Despite the importance of these proteins, the molecular basis of their effects on T cells is poorly understood. It remains unclear how Tip and StpC affect gene expression and what is the molecular basis of their cooperation. To address these issues, we expressed Tip and StpC in T lymphoblastoid cells and assessed both their effects on and transcription factors involved in IL-2 gene expression. Our study shows that Tip and StpC cooperate to upregulate IL-2 gene expression, that their effect is mediated primarily by NF-κB and NF-AT, which is partially dependent on tyrosine phosphorylation.
E A De Wynter - One of the best experts on this subject based on the ideXlab platform.
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Marker gene transfer into human haemopoietic cells using a Herpesvirus saimiri-based vector
Gene Therapy, 2005Co-Authors: G M Doody, J P Leek, A K Bali, A Ensser, A F Markham, E A De WynterAbstract:Herpesvirus-based gene therapy vectors offer an attractive alternative to retroviral vectors because of their episomal nature and ability to accommodate large transgenes. Saimiriine Herpesvirus 2 (HVS) is a prototypical gamma-2 Herpesvirus that can latently infect numerous different cell types. A cosmid-generated HVS vector in which transforming genes have been deleted and the marker gene encoding enhanced green fluorescent protein (HVS-GFP) has been incorporated was evaluated for its potential to transduce CD34+ haemopoietic progenitors selected from cord blood. Expression of GFP could subsequently be readily detected in cells of the erythroid lineage in both CFU-GEMM assays and liquid differentiation cultures. These results confirm the potential of HVS as a candidate vector for gene therapy applications using primitive haemopoietic cells and suggest that it may be applicable to disorders affecting cells of the erythroid lineage.
G M Doody - One of the best experts on this subject based on the ideXlab platform.
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Marker gene transfer into human haemopoietic cells using a Herpesvirus saimiri-based vector
Gene Therapy, 2005Co-Authors: G M Doody, J P Leek, A K Bali, A Ensser, A F Markham, E A De WynterAbstract:Herpesvirus-based gene therapy vectors offer an attractive alternative to retroviral vectors because of their episomal nature and ability to accommodate large transgenes. Saimiriine Herpesvirus 2 (HVS) is a prototypical gamma-2 Herpesvirus that can latently infect numerous different cell types. A cosmid-generated HVS vector in which transforming genes have been deleted and the marker gene encoding enhanced green fluorescent protein (HVS-GFP) has been incorporated was evaluated for its potential to transduce CD34+ haemopoietic progenitors selected from cord blood. Expression of GFP could subsequently be readily detected in cells of the erythroid lineage in both CFU-GEMM assays and liquid differentiation cultures. These results confirm the potential of HVS as a candidate vector for gene therapy applications using primitive haemopoietic cells and suggest that it may be applicable to disorders affecting cells of the erythroid lineage.
Muneer G. Hasham - One of the best experts on this subject based on the ideXlab platform.
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Tip, an Lck-interacting protein of Herpesvirus saimiri, causes Fas- and Lck-dependent apoptosis of T lymphocytes
Virology, 2004Co-Authors: Muneer G. Hasham, Alexander Y. TsygankovAbstract:Saimiriine Herpesvirus-2 (Herpesvirus saimiri) transforms T lymphocytes, including human, to continuous growth in vitro. H. saimiri-induced transformation is becoming an important tool of T-cell biology, including studies of HIV replication. Two proteins of H. saimiri subgroup C, Tip and StpC, are essential for T-cell transformation. In spite of the important role of these proteins, their biological functions and the molecular mechanisms of their action remain insufficiently understood. To further elucidate the effects of Tip on T cells, we transduced T lymphocytes, using an efficient lentiviral gene transfer system, to express Tip in the absence of other H. saimiri proteins. Our results indicate that Tip specifically inhibits IL-2 production by human T lymphocytes. Furthermore, Tip promotes T-cell apoptosis, which appears to be the reason for the observed decrease in IL-2 production. Finally, the apoptotic effect of Tip in T cells is mediated by Fas and requires the presence of active Lck in the cell.
