The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Shinji Makino - One of the best experts on this subject based on the ideXlab platform.
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Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal
Journal of Virology, 2003Co-Authors: Krishna Narayanan, Junko Maeda, Chun-jen Chen, Shinji MakinoAbstract:For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) Protein is the first step described in the process of viral RNA packaging. In the Murine coronavirus a selective interaction between the viral transMeMbrane envelope Protein M and the viral ribonucleoProtein coMplex, coMposed of N Protein and viral RNA containing a short cis-acting RNA eleMent, the packaging signal, deterMines the selective RNA packaging into virus particles. In this report we show that expressed coronavirus envelope Protein M specifically interacted with coexpressed noncoronavirus RNA transcripts containing the short viral packaging signal in the absence of coronavirus N Protein. FurtherMore, this M Protein-packaging signal interaction led to specific packaging of the packaging signal-containing RNA transcripts into coronavirus-like particles in the absence of N Protein. These findings not only highlight a novel RNA packaging MechanisM for an enveloped virus, where the specific RNA packaging can occur without the core or N Protein, but also point to a new, biologically iMportant general Model of precise and selective interaction between transMeMbrane Proteins and specific RNA eleMents.
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induction of apoptosis in Murine coronavirus infected cultured cells and deMonstration of e Protein as an apoptosis inducer
Journal of Virology, 1999Co-Authors: Julian L Leibowitz, Chun-jen Chen, Shinji MakinoAbstract:We deMonstrated that infection of 17Cl-1 cells with the Murine coronavirus Mouse hepatitis virus (MHV) induced caspase-dependent apoptosis. MHV-infected DBT cells did not show apoptotic changes, indicating that apoptosis was not a universal MechanisM of cell death in MHV-infected cells. Expression of MHV structural Proteins by recoMbinant vaccinia viruses showed that expression of MHV E Protein induced apoptosis in DBT cells, whereas expression of other MHV structural Proteins, including S Protein, M Protein, N Protein, and heMagglutinin-esterase Protein, failed to induce apoptosis. MHV E Protein-Mediated apoptosis was suppressed by a high level of Bcl-2 oncogene expression. Our data showed that MHV E Protein is a Multifunctional Protein; in addition to its known function in coronavirus envelope forMation, it also induces apoptosis.
John M. Sanderson - One of the best experts on this subject based on the ideXlab platform.
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surface features of a Mononegavirales Matrix Protein indicate sites of MeMbrane interaction
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: V A Money, Helen K. Mcphee, Jackie A Mosely, John M. SandersonAbstract:The Matrix Protein (M) of respiratory syncytial virus (RSV), the prototype viral MeMber of the PneuMovirinae (faMily ParaMyxoviridae, order Mononegavirales), has been crystallized and the structure deterMined to a resolution of 1.6 Å. The structure coMprises 2 coMpact β-rich doMains connected by a relatively unstructured linker region. Due to the high degree of side-chain order in the structure, an extensive contiguous area of positive surface charge covering ≈600 Å2 can be resolved. This unusually large patch of positive surface potential spans both doMains and the linker, and provides a MechanisM for driving the interaction of the Protein with a negatively-charged MeMbrane surface or other virion coMponents such as the nucleocapsid. This patch is coMpleMented by regions of high hydrophobicity and a striking planar arrangeMent of tyrosine residues encircling the C-terMinal doMain. CoMparison of the RSV M sequence with other MeMbers of the PneuMovirinae shows that regions of divergence correspond to surface exposed loops in the M structure, with the Majority of viral species-specific differences occurring in the N-terMinal doMain.
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Surface features of a Mononegavirales Matrix Protein indicate sites of MeMbrane interaction
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: V A Money, Helen K. Mcphee, John M. Sanderson, Jackie A Mosely, Robert P. YeoAbstract:The Matrix Protein (M) of respiratory syncytial virus (RSV), the prototype viral MeMber of the PneuMovirinae (faMily ParaMyxoviridae, order Mononegavirales), has been crystallized and the structure deterMined to a resolution of 1.6 A. The structure coMprises 2 coMpact beta-rich doMains connected by a relatively unstructured linker region. Due to the high degree of side-chain order in the structure, an extensive contiguous area of positive surface charge covering approxiMately 600 A(2) can be resolved. This unusually large patch of positive surface potential spans both doMains and the linker, and provides a MechanisM for driving the interaction of the Protein with a negatively-charged MeMbrane surface or other virion coMponents such as the nucleocapsid. This patch is coMpleMented by regions of high hydrophobicity and a striking planar arrangeMent of tyrosine residues encircling the C-terMinal doMain. CoMparison of the RSV M sequence with other MeMbers of the PneuMovirinae shows that regions of divergence correspond to surface exposed loops in the M structure, with the Majority of viral species-specific differences occurring in the N-terMinal doMain.
V A Money - One of the best experts on this subject based on the ideXlab platform.
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surface features of a Mononegavirales Matrix Protein indicate sites of MeMbrane interaction
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: V A Money, Helen K. Mcphee, Jackie A Mosely, John M. SandersonAbstract:The Matrix Protein (M) of respiratory syncytial virus (RSV), the prototype viral MeMber of the PneuMovirinae (faMily ParaMyxoviridae, order Mononegavirales), has been crystallized and the structure deterMined to a resolution of 1.6 Å. The structure coMprises 2 coMpact β-rich doMains connected by a relatively unstructured linker region. Due to the high degree of side-chain order in the structure, an extensive contiguous area of positive surface charge covering ≈600 Å2 can be resolved. This unusually large patch of positive surface potential spans both doMains and the linker, and provides a MechanisM for driving the interaction of the Protein with a negatively-charged MeMbrane surface or other virion coMponents such as the nucleocapsid. This patch is coMpleMented by regions of high hydrophobicity and a striking planar arrangeMent of tyrosine residues encircling the C-terMinal doMain. CoMparison of the RSV M sequence with other MeMbers of the PneuMovirinae shows that regions of divergence correspond to surface exposed loops in the M structure, with the Majority of viral species-specific differences occurring in the N-terMinal doMain.
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Surface features of a Mononegavirales Matrix Protein indicate sites of MeMbrane interaction
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: V A Money, Helen K. Mcphee, John M. Sanderson, Jackie A Mosely, Robert P. YeoAbstract:The Matrix Protein (M) of respiratory syncytial virus (RSV), the prototype viral MeMber of the PneuMovirinae (faMily ParaMyxoviridae, order Mononegavirales), has been crystallized and the structure deterMined to a resolution of 1.6 A. The structure coMprises 2 coMpact beta-rich doMains connected by a relatively unstructured linker region. Due to the high degree of side-chain order in the structure, an extensive contiguous area of positive surface charge covering approxiMately 600 A(2) can be resolved. This unusually large patch of positive surface potential spans both doMains and the linker, and provides a MechanisM for driving the interaction of the Protein with a negatively-charged MeMbrane surface or other virion coMponents such as the nucleocapsid. This patch is coMpleMented by regions of high hydrophobicity and a striking planar arrangeMent of tyrosine residues encircling the C-terMinal doMain. CoMparison of the RSV M sequence with other MeMbers of the PneuMovirinae shows that regions of divergence correspond to surface exposed loops in the M structure, with the Majority of viral species-specific differences occurring in the N-terMinal doMain.
Hervé Lecoeur - One of the best experts on this subject based on the ideXlab platform.
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A flavivirus Protein M-derived peptide directly perMeabilizes Mitochondrial MeMbranes, triggers cell death and reduces huMan tuMor growth in nude Mice.
Apoptosis, 2009Co-Authors: Magali Brabant, Ludwig Baux, Richard Casimir, Jean Paul Briand, Olivier Chaloin, Mathieu Porceddu, Nelly Buron, David Chauvier, Myriam Lassalle, Hervé LecoeurAbstract:Dengue viruses belong to the Flavivirus faMily and are responsible for heMorrhagic fever in HuMan. Dengue virus infection triggers apoptosis especially through the expression of the sMall MeMbrane (M) Protein. Using isolated Mitochondria, we found that synthetic peptides containing the C-terMinus part of the M ectodoMain caused apoptosis-related Mitochondrial MeMbrane perMeabilization (MMP) events. These events include Matrix swelling and the dissipation of the Mitochondrial transMeMbrane potential (DeltaPsi(M)). Protein M Flavivirus sequence alignMents and helical wheel projections reveal a conserved distribution of charged residues. Moreover, when coMbined to the cell penetrating HIV-1 Tat peptide transduction doMain (Tat-PTD), this sequence triggers a caspase-dependent cell death associated with DeltaPsi(M) loss and cytochroMe c release. Mutational approaches coupled to functional screening on isolated Mitochondria resulted in the selection of a Protein M derived sequence containing nine residues with potent MMP-inducing properties on isolated Mitochondria. A chiMeric peptide coMposed of a Tat-PTD linked to the 9-Mer entity triggers MMP and cell death. Finally, local adMinistration of this chiMeric peptide induces growth inhibition of xenograft prostate PC3 tuMors in iMMuno-coMproMised Mice, and significantly enhances aniMal survival. Together, these findings support the notion of using viral genoMes as valuable sources to discover Mitochondria-targeted sequences that May lead to the developMent of new anticancer coMpounds.
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A flavivirus Protein M-derived peptide directly perMeabilizes Mitochondrial MeMbranes, triggers cell death and reduces huMan tuMor growth in nude Mice
Apoptosis, 2009Co-Authors: Magali Brabant, Ludwig Baux, Richard Casimir, Jean Paul Briand, Olivier Chaloin, Mathieu Porceddu, Nelly Buron, David Chauvier, Myriam Lassalle, Hervé LecoeurAbstract:Dengue viruses belong to the Flavivirus faMily and are responsible for heMorrhagic fever in HuMan. Dengue virus infection triggers apoptosis especially through the expression of the sMall MeMbrane (M) Protein. Using isolated Mitochondria, we found that synthetic peptides containing the C-terMinus part of the M ectodoMain caused apoptosis-related Mitochondrial MeMbrane perMeabilization (MMP) events. These events include Matrix swelling and the dissipation of the Mitochondrial transMeMbrane potential (ΔΨ_M). Protein M Flavivirus sequence alignMents and helical wheel projections reveal a conserved distribution of charged residues. Moreover, when coMbined to the cell penetrating HIV-1 Tat peptide transduction doMain (Tat-PTD), this sequence triggers a caspase-dependent cell death associated with ΔΨ_M loss and cytochroMe c release. Mutational approaches coupled to functional screening on isolated Mitochondria resulted in the selection of a Protein M derived sequence containing nine residues with potent MMP-inducing properties on isolated Mitochondria. A chiMeric peptide coMposed of a Tat-PTD linked to the 9-Mer entity triggers MMP and cell death. Finally, local adMinistration of this chiMeric peptide induces growth inhibition of xenograft prostate PC3 tuMors in iMMuno-coMproMised Mice, and significantly enhances aniMal survival. Together, these findings support the notion of using viral genoMes as valuable sources to discover Mitochondria-targeted sequences that May lead to the developMent of new anticancer coMpounds.
Chun-jen Chen - One of the best experts on this subject based on the ideXlab platform.
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Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal
Journal of Virology, 2003Co-Authors: Krishna Narayanan, Junko Maeda, Chun-jen Chen, Shinji MakinoAbstract:For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) Protein is the first step described in the process of viral RNA packaging. In the Murine coronavirus a selective interaction between the viral transMeMbrane envelope Protein M and the viral ribonucleoProtein coMplex, coMposed of N Protein and viral RNA containing a short cis-acting RNA eleMent, the packaging signal, deterMines the selective RNA packaging into virus particles. In this report we show that expressed coronavirus envelope Protein M specifically interacted with coexpressed noncoronavirus RNA transcripts containing the short viral packaging signal in the absence of coronavirus N Protein. FurtherMore, this M Protein-packaging signal interaction led to specific packaging of the packaging signal-containing RNA transcripts into coronavirus-like particles in the absence of N Protein. These findings not only highlight a novel RNA packaging MechanisM for an enveloped virus, where the specific RNA packaging can occur without the core or N Protein, but also point to a new, biologically iMportant general Model of precise and selective interaction between transMeMbrane Proteins and specific RNA eleMents.
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induction of apoptosis in Murine coronavirus infected cultured cells and deMonstration of e Protein as an apoptosis inducer
Journal of Virology, 1999Co-Authors: Julian L Leibowitz, Chun-jen Chen, Shinji MakinoAbstract:We deMonstrated that infection of 17Cl-1 cells with the Murine coronavirus Mouse hepatitis virus (MHV) induced caspase-dependent apoptosis. MHV-infected DBT cells did not show apoptotic changes, indicating that apoptosis was not a universal MechanisM of cell death in MHV-infected cells. Expression of MHV structural Proteins by recoMbinant vaccinia viruses showed that expression of MHV E Protein induced apoptosis in DBT cells, whereas expression of other MHV structural Proteins, including S Protein, M Protein, N Protein, and heMagglutinin-esterase Protein, failed to induce apoptosis. MHV E Protein-Mediated apoptosis was suppressed by a high level of Bcl-2 oncogene expression. Our data showed that MHV E Protein is a Multifunctional Protein; in addition to its known function in coronavirus envelope forMation, it also induces apoptosis.
