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Barbara S. Coulson - One of the best experts on this subject based on the ideXlab platform.
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rotavirus replication in intestinal cells differentially regulates Integrin expression by a phosphatidylinositol 3 kinase dependent pathway resulting in increased cell adhesion and virus yield
Journal of Virology, 2008Co-Authors: Peter Halasz, Gavan Holloway, Stephen J. Turner, Barbara S. CoulsonAbstract:Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface Integrins with the extracellular matrix. In this study, we detected alterations in cellular Integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 Integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 Integrins, if present, was down-regulated. This differential regulation of Integrins was reflected at the transcriptional level. It was unrelated to the use of Integrins as rotavirus receptors, as both Integrin-using and Integrin-independent viruses induced Integrin regulation. Using pharmacological agents that inhibit kinase activity, Integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of Integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of Integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
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rotavirus replication in intestinal cells differentially regulates Integrin expression by a phosphatidylinositol 3 kinase dependent pathway resulting in increased cell adhesion and virus yield
Journal of Virology, 2008Co-Authors: Peter Halasz, Gavan Holloway, Stephen J. Turner, Barbara S. CoulsonAbstract:Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface Integrins with the extracellular matrix. In this study, we detected alterations in cellular Integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 Integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 Integrins, if present, was down-regulated. This differential regulation of Integrins was reflected at the transcriptional level. It was unrelated to the use of Integrins as rotavirus receptors, as both Integrin-using and Integrin-independent viruses induced Integrin regulation. Using pharmacological agents that inhibit kinase activity, Integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of Integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of Integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
Peter Halasz - One of the best experts on this subject based on the ideXlab platform.
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rotavirus replication in intestinal cells differentially regulates Integrin expression by a phosphatidylinositol 3 kinase dependent pathway resulting in increased cell adhesion and virus yield
Journal of Virology, 2008Co-Authors: Peter Halasz, Gavan Holloway, Stephen J. Turner, Barbara S. CoulsonAbstract:Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface Integrins with the extracellular matrix. In this study, we detected alterations in cellular Integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 Integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 Integrins, if present, was down-regulated. This differential regulation of Integrins was reflected at the transcriptional level. It was unrelated to the use of Integrins as rotavirus receptors, as both Integrin-using and Integrin-independent viruses induced Integrin regulation. Using pharmacological agents that inhibit kinase activity, Integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of Integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of Integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
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rotavirus replication in intestinal cells differentially regulates Integrin expression by a phosphatidylinositol 3 kinase dependent pathway resulting in increased cell adhesion and virus yield
Journal of Virology, 2008Co-Authors: Peter Halasz, Gavan Holloway, Stephen J. Turner, Barbara S. CoulsonAbstract:Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface Integrins with the extracellular matrix. In this study, we detected alterations in cellular Integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 Integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 Integrins, if present, was down-regulated. This differential regulation of Integrins was reflected at the transcriptional level. It was unrelated to the use of Integrins as rotavirus receptors, as both Integrin-using and Integrin-independent viruses induced Integrin regulation. Using pharmacological agents that inhibit kinase activity, Integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of Integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of Integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
Erich R Mackow - One of the best experts on this subject based on the ideXlab platform.
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pathogenic hantaviruses selectively inhibit beta3 Integrin directed endothelial cell migration
Archives of Virology, 2002Co-Authors: Irina N Gavrilovskaya, Erika Geimonen, T Peresleni, Erich R MackowAbstract:Hantaviruses cause two diseases of man, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Pathogenic and non-pathogenic hantaviruses use β3 and β1 Integrins, respectively, to enter endothelial cells. β3 Integrins were recently reported to bind receptors that regulate vascular permeability suggesting that hantavirus β3 Integrin interactions may regulate endothelial cell function and contribute to viral pathogenesis. In this study we investigated the ability of pathogenic and non-pathogenic hantaviruses to regulate β3 and β1 Integrin directed endothelial cell functions. We found that pathogenic NY-1, SNV, HTN, SEO and PUU viruses blocked endothelial cell migration on β3, but not β1, Integrin ligands. Migration is similarly inhibited by antibodies to β3 Integrins which selectively block vitronectin directed endothelial cell migration. As a result, the ability of endothelial cells to migrate on Integrin ligands was selectively inhibited by only pathogenic hantaviruses. Infection by NY-1 virus inhibited endothelial cell migration as early as 24–48 h post-infection. In contrast, non-pathogenic PH and TUL viruses had no effect on the ability of endothelial cells to migrate on either β3 or β1 Integrin ligands from 1 to 5 days post-infection. These findings indicate that only hantaviruses which use β3 Integrins, and are associated with HPS and HFRS diseases, functionally dysregulate endothelial cell migration. These findings further demonstrate that hantaviruses regulate only β3 Integrin directed endothelial cell functions and have no effect on β1 Integrin functions. Since β3 Integrins are linked to changes in vascular permeability and the maintenance of vascular integrity, these findings suggest a means by which hantavirus usage and regulation of β3 Integrins may contribute to hantavirus pathogenesis.
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cellular entry of hantaviruses which cause hemorrhagic fever with renal syndrome is mediated by beta3 Integrins
Journal of Virology, 1999Co-Authors: Irina N Gavrilovskaya, Erich R Mackow, Mark H Ginsberg, Eric J BrownAbstract:Hantaviruses replicate primarily in the vascular endothelium and cause two human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). In this report, we demonstrate that the cellular entry of HFRS-associated hantaviruses is facilitated by specific Integrins expressed on platelets, endothelial cells, and macrophages. Infection of human umbilical vein endothelial cells and Vero E6 cells by the HFRS-causing hantaviruses Hantaan (HTN), Seoul (SEO), and Puumala (PUU) is inhibited by antibodies to alphavbeta3 Integrins and by the Integrin ligand vitronectin. The cellular entry of HTN, SEO, and PUU viruses, but not the nonpathogenic Prospect Hill (PH) hantavirus (i.e., a virus with no associated human disease), was also mediated by introducting recombinant alphaIIbbeta3 or alphavbeta3 Integrins into beta3-Integrin-deficient CHO cells. In addition, PH infectivity was not inhibited by alphavbeta3-specific sera or vitronectin but was blocked by alpha5beta1-specific sera and the Integrin ligand fibronectin. RGD tripeptides, which are required for many Integrin-ligand interactions, are absent from all hantavirus G1 and G2 surface glycoproteins, and GRGDSP peptides did not inhibit hantavirus infectivity. Further, a mouse-human hybrid beta3 Integrin-specific Fab fragment, c7E3 (ReoPro), also inhibited the infectivity of HTN, SEO, and PUU as well as HPS-associated hantaviruses, Sin Nombre (SN) and New York-1 (NY-1). These findings indicate that pathogenic HPS- and HFRS-causing hantaviruses enter cells via beta3 Integrins, which are present on the surfaces of platelets, endothelial cells, and macrophages. Since beta3 Integrins regulate vascular permeability and platelet function, these findings also correlate beta3 Integrin usage with common elements of hantavirus pathogenesis.
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β3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Irina N Gavrilovskaya, Michael Shepley, Robert Shaw, Mark H Ginsberg, Erich R MackowAbstract:Newly emerged hantaviruses replicate primarily in the pulmonary endothelium, cause acute platelet loss, and result in hantavirus pulmonary syndrome (HPS). We now report that specific Integrins expressed on platelets and endothelial cells permit the cellular entry of HPS-associated hantaviruses. Infection with HPS-associated hantaviruses, NY-1 and Sin Nombre virus (SNV), is inhibited by antibodies to β3 Integrins and by the β3-Integrin ligand, vitronectin. In contrast, infection with the nonpathogenic (no associated human disease) Prospect Hill virus was inhibited by fibronectin and β1-specific antibodies but not by β3-specific antibodies or vitronectin. Transfection with recombinant αIIbβ3 or αvβ3 Integrins rendered cells permissive to NY-1 and SNV but not Prospect Hill virus infection, indicating that αIIbβ3 and αvβ3 Integrins mediate the entry of NY-1 and SNV hantaviruses. Furthermore, entry is divalent cation independent, not blocked by arginine-glycine-aspartic acid peptides and still mediated by, ligand-binding defective, αIIbβ3-Integrin mutants. Hence, NY-1 and SNV entry is independent of β3 Integrin binding to physiologic ligands. These findings implicate Integrins as cellular receptors for hantaviruses and indicate that hantavirus pathogenicity correlates with Integrin usage.
Gavan Holloway - One of the best experts on this subject based on the ideXlab platform.
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rotavirus replication in intestinal cells differentially regulates Integrin expression by a phosphatidylinositol 3 kinase dependent pathway resulting in increased cell adhesion and virus yield
Journal of Virology, 2008Co-Authors: Peter Halasz, Gavan Holloway, Stephen J. Turner, Barbara S. CoulsonAbstract:Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface Integrins with the extracellular matrix. In this study, we detected alterations in cellular Integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 Integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 Integrins, if present, was down-regulated. This differential regulation of Integrins was reflected at the transcriptional level. It was unrelated to the use of Integrins as rotavirus receptors, as both Integrin-using and Integrin-independent viruses induced Integrin regulation. Using pharmacological agents that inhibit kinase activity, Integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of Integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of Integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
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rotavirus replication in intestinal cells differentially regulates Integrin expression by a phosphatidylinositol 3 kinase dependent pathway resulting in increased cell adhesion and virus yield
Journal of Virology, 2008Co-Authors: Peter Halasz, Gavan Holloway, Stephen J. Turner, Barbara S. CoulsonAbstract:Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface Integrins with the extracellular matrix. In this study, we detected alterations in cellular Integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 Integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 Integrins, if present, was down-regulated. This differential regulation of Integrins was reflected at the transcriptional level. It was unrelated to the use of Integrins as rotavirus receptors, as both Integrin-using and Integrin-independent viruses induced Integrin regulation. Using pharmacological agents that inhibit kinase activity, Integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of Integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of Integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
Stephen J. Turner - One of the best experts on this subject based on the ideXlab platform.
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rotavirus replication in intestinal cells differentially regulates Integrin expression by a phosphatidylinositol 3 kinase dependent pathway resulting in increased cell adhesion and virus yield
Journal of Virology, 2008Co-Authors: Peter Halasz, Gavan Holloway, Stephen J. Turner, Barbara S. CoulsonAbstract:Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface Integrins with the extracellular matrix. In this study, we detected alterations in cellular Integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 Integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 Integrins, if present, was down-regulated. This differential regulation of Integrins was reflected at the transcriptional level. It was unrelated to the use of Integrins as rotavirus receptors, as both Integrin-using and Integrin-independent viruses induced Integrin regulation. Using pharmacological agents that inhibit kinase activity, Integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of Integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of Integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
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rotavirus replication in intestinal cells differentially regulates Integrin expression by a phosphatidylinositol 3 kinase dependent pathway resulting in increased cell adhesion and virus yield
Journal of Virology, 2008Co-Authors: Peter Halasz, Gavan Holloway, Stephen J. Turner, Barbara S. CoulsonAbstract:Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface Integrins with the extracellular matrix. In this study, we detected alterations in cellular Integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 Integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 Integrins, if present, was down-regulated. This differential regulation of Integrins was reflected at the transcriptional level. It was unrelated to the use of Integrins as rotavirus receptors, as both Integrin-using and Integrin-independent viruses induced Integrin regulation. Using pharmacological agents that inhibit kinase activity, Integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of Integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of Integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
