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Patrick L. Green - One of the best experts on this subject based on the ideXlab platform.
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human t lymphotropic virus type 1 su residue 195 plays a role in determining the preferential cd4 t Cell Immortalization transformation tropism
Journal of Virology, 2013Co-Authors: Priya Kannian, Soledad Fernandez, Kathryn S. Jones, Patrick L. GreenAbstract:Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T Cell leukemia and predominantly immortalizes/transforms CD4+ T Cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+ T Cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T Cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the Cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the Immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear Cells in culture. HTLV-1/SU2 shifted the CD4+ T Cell Immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+ T Cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T Cell Immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T Cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T Cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T Cell Immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+ T Cell Immortalization tropism. The slower emergence of the CD8+ T Cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
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Human T Lymphotropic Virus Type 1 SU Residue 195 Plays a Role in Determining the Preferential CD4+ T Cell Immortalization/Transformation Tropism
Journal of virology, 2013Co-Authors: Priya Kannian, Soledad Fernandez, Kathryn S. Jones, Patrick L. GreenAbstract:Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T Cell leukemia and predominantly immortalizes/transforms CD4+ T Cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+ T Cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T Cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the Cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the Immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear Cells in culture. HTLV-1/SU2 shifted the CD4+ T Cell Immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+ T Cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T Cell Immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T Cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T Cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T Cell Immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+ T Cell Immortalization tropism. The slower emergence of the CD8+ T Cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
Priya Kannian - One of the best experts on this subject based on the ideXlab platform.
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human t lymphotropic virus type 1 su residue 195 plays a role in determining the preferential cd4 t Cell Immortalization transformation tropism
Journal of Virology, 2013Co-Authors: Priya Kannian, Soledad Fernandez, Kathryn S. Jones, Patrick L. GreenAbstract:Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T Cell leukemia and predominantly immortalizes/transforms CD4+ T Cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+ T Cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T Cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the Cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the Immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear Cells in culture. HTLV-1/SU2 shifted the CD4+ T Cell Immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+ T Cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T Cell Immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T Cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T Cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T Cell Immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+ T Cell Immortalization tropism. The slower emergence of the CD8+ T Cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
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Human T Lymphotropic Virus Type 1 SU Residue 195 Plays a Role in Determining the Preferential CD4+ T Cell Immortalization/Transformation Tropism
Journal of virology, 2013Co-Authors: Priya Kannian, Soledad Fernandez, Kathryn S. Jones, Patrick L. GreenAbstract:Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T Cell leukemia and predominantly immortalizes/transforms CD4+ T Cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+ T Cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T Cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the Cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the Immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear Cells in culture. HTLV-1/SU2 shifted the CD4+ T Cell Immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+ T Cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T Cell Immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T Cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T Cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T Cell Immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+ T Cell Immortalization tropism. The slower emergence of the CD8+ T Cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
Soledad Fernandez - One of the best experts on this subject based on the ideXlab platform.
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human t lymphotropic virus type 1 su residue 195 plays a role in determining the preferential cd4 t Cell Immortalization transformation tropism
Journal of Virology, 2013Co-Authors: Priya Kannian, Soledad Fernandez, Kathryn S. Jones, Patrick L. GreenAbstract:Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T Cell leukemia and predominantly immortalizes/transforms CD4+ T Cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+ T Cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T Cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the Cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the Immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear Cells in culture. HTLV-1/SU2 shifted the CD4+ T Cell Immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+ T Cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T Cell Immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T Cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T Cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T Cell Immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+ T Cell Immortalization tropism. The slower emergence of the CD8+ T Cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
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Human T Lymphotropic Virus Type 1 SU Residue 195 Plays a Role in Determining the Preferential CD4+ T Cell Immortalization/Transformation Tropism
Journal of virology, 2013Co-Authors: Priya Kannian, Soledad Fernandez, Kathryn S. Jones, Patrick L. GreenAbstract:Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T Cell leukemia and predominantly immortalizes/transforms CD4+ T Cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+ T Cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T Cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the Cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the Immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear Cells in culture. HTLV-1/SU2 shifted the CD4+ T Cell Immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+ T Cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T Cell Immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T Cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T Cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T Cell Immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+ T Cell Immortalization tropism. The slower emergence of the CD8+ T Cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
Kathryn S. Jones - One of the best experts on this subject based on the ideXlab platform.
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human t lymphotropic virus type 1 su residue 195 plays a role in determining the preferential cd4 t Cell Immortalization transformation tropism
Journal of Virology, 2013Co-Authors: Priya Kannian, Soledad Fernandez, Kathryn S. Jones, Patrick L. GreenAbstract:Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T Cell leukemia and predominantly immortalizes/transforms CD4+ T Cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+ T Cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T Cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the Cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the Immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear Cells in culture. HTLV-1/SU2 shifted the CD4+ T Cell Immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+ T Cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T Cell Immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T Cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T Cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T Cell Immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+ T Cell Immortalization tropism. The slower emergence of the CD8+ T Cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
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Human T Lymphotropic Virus Type 1 SU Residue 195 Plays a Role in Determining the Preferential CD4+ T Cell Immortalization/Transformation Tropism
Journal of virology, 2013Co-Authors: Priya Kannian, Soledad Fernandez, Kathryn S. Jones, Patrick L. GreenAbstract:Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T Cell leukemia and predominantly immortalizes/transforms CD4+ T Cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+ T Cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T Cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the Cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the Immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear Cells in culture. HTLV-1/SU2 shifted the CD4+ T Cell Immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+ T Cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T Cell Immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T Cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T Cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T Cell Immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+ T Cell Immortalization tropism. The slower emergence of the CD8+ T Cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
Wolfgang Hammerschmidt - One of the best experts on this subject based on the ideXlab platform.
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the ebv nuclear antigen 1 ebna1 enhances b Cell Immortalization several thousandfold
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Sibille Humme, Wolfgang Hammerschmidt, Gilbert Reisbach, Regina Feederle, Henri Jacques Delecluse, Kristine Bousset, Aloys SchepersAbstract:The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is one of the earliest viral proteins expressed after infection and is the only latent protein consistently expressed in viral-associated tumors. EBNA1's crucial role in viral DNA replication, episomal maintenance, and partitioning is well examined whereas its importance for the Immortalization process and the tumorgenicity of EBV is unclear. To address these open questions, we generated, based on the maxi-EBV system, an EBNA1-deficient EBV mutant and used this strain to infect primary human B Cells. Surprisingly, lymphoblastoid Cell lines (LCL) emerged from these experiments, although with very low frequency. These Cell lines were indistinguishable from normal LCLs with respect to proliferation and growth conditions. A detailed analysis indicated that the entire viral DNA was integrated into the Cellular genome. At least 5 of the 11 latent EBV proteins were expressed, indicating the integrity of the EBV genome. EBNA1-positive and DeltaEBNA1-EBV-LCLs were injected into severe combined immunodeficient (SCID) mice to examine their tumorgenicity in comparison. Both groups supported tumor growth, indicating that EBNA1 is not mandatory for EBV's oncogenic potential. The results shown provide genetic evidence that EBNA1 is not essential to establish LCLs but promotes the efficiency of this process significantly.
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Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B Cells but both it and activated CD40 can prolong their survival.
The EMBO journal, 1996Co-Authors: Ursula Zimber-strobl, Bettina Kempkes, Georg W. Bornkamm, Gabriele Marschall, Reinhard Zeidler, C Van Kooten, J Banchereau, Wolfgang HammerschmidtAbstract:Epstein-Barr virus (EBV) infects human primary B lymphocytes and induces and maintains proliferation of these Cells efficiently in vitro. Mutants of Epstein-Barr virus which express EBV nuclear antigen 2 (EBNA2) in a conditional fashion allow dissection of individual contributions of viral genes to B Cell Immortalization. EBNA2 is a transcriptional activator of Cellular and viral genes, including the viral latent membrane protein 1 (LMP1), which is essential for B Cell Immortalization and has oncogenic effects in non-lymphoid Cells. To analyze the role of this gene in B Cell Immortalization, LMP1 was constitutively expressed in B Cells infected with EBV carrying a conditional EBNA2 allele. In the absence of functional EBNA2, LMP1 was incapable of sustaining B Cell proliferation in two independent assays but induced a phenotype consistent with prolonged Cell viability. Activation of CD40 displayed a comparable phenotype. These data indicate that both CD40 activation and LMP1 expression may use a common pathway for B Cell activation. Proliferation of human B Cells, however, requires one or more additional signals triggered by EBNA2.
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The latent membrane protein 2 gene of Epstein-Barr virus is important for efficient B Cell Immortalization
Journal of General Virology, 1996Co-Authors: Markus Brielmeier, Josef Mautner, Gerhard Laux, Wolfgang HammerschmidtAbstract:The viral latent membrane proteins 2 (LMP2) of Epstein—Barr virus (EBV) were analysed genetically to evaluate their role in B Cell Immortalization. LMP2 is transcribed as two differently spliced mRNAs which code for the LMP2A and -B proteins, also called terminal protein-1 and -2. LMP2A and -B are found in latently infected, growth-transformed B lymphocytes in vitro, in different human tumours, and in latently infected B Cells in vivo. Two different approaches were used to generate EBV mutants in which the second, third and part of the fourth exon of the LMP2 gene were deleted by insertion of a marker gene. Initially, conventional homologous recombination in a Burkitt's lymphoma Cell line (P3HR1) between the endogenous EBV genome and an introduced plasmid was used to generate EBV mutants. This experiment identified LMP2 as dispensable for B Cell Immortalization as has been reported. In a second approach, the same LMP2 mutant gene was analysed in the context of a mini-EBV plasmid. These are E. coli constructs that are sufficient when packaged into an EBV coat both to initiate and to maintain proliferation of infected B Cells. In comparison with a fully competent mini-EBV, LMP2- mini-EBVs were found to be greatly reduced in their capacity to yield immortalized B Cell clones. This finding confirmed the initially observed bias against LMP2- B Cell clones, most of which were found to be coinfected with complementing P3HR1 virus. These results indicate that LMP2 contributes to the efficiency of B Cell Immortalization and that the LMP2s phenotype is auxiliary in nature.