Alteration in the expression of endothelial cell integrin receptors α5β1 and α2β1 and α6β1 after in vitro infection with a clinical isolate of human cytomegalovirus

Shahgasempour, Shapour; Woodroffe, S. B.; Sullivan-Tailyour, G.; Garnett, Helen M.

doi:10.1007/s007050050063

Cited by 26 publications

(22 citation statements)

References 19 publications

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“…HCMV infection also alters cell cycle regulation (27,53,54), cell adhesion molecule (76) and transcription factor expression and activities (36), and influences genes that can be involved in oncogenesis (7). Each of the two clusters of host genes that responded to HCMV infection in the present study included genes encoding proteins that participate in each of these processes, which we discuss below.…”

Section: Discussionmentioning

confidence: 95%

“…By negatively impacting these cellular functions in the immune system, decreased expression of adhesion molecules in response to HCMV infection would severely compromise the host response to the infection. Several studies support this idea; for example, HCMV infection of human endothelial cells (76) and human fibroblasts (93) altered the expression of the integrin ␤1-subunit. Another report showed that integrin activation of cyclin-dependent kinases 2 and 6 was necessary for cells to progress through G 1 of the cell cycle and also for the expression of cyclin D1 (24).…”

Section: Discussionmentioning

confidence: 95%

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Evaluation of the host transcriptional response to human cytomegalovirus infection

Challacombe

Rechtsteiner

Gottardo

et al. 2004

Physiological Genomics

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Gene expression data from human cytomegalovirus (HCMV)-infected cells were analyzed using DNA-Chip Analyzer (dChip) followed by singular value decomposition (SVD) and compared with a previous analysis of the same data that employed GeneChip software and a fold change filtering approach. dChip and SVD analysis revealed two clusters of coexpressed human genes responding differently to HCMV infection: one containing some genes identified previously, and another that was largely unique to this analysis. Annotating these genes, we identified several functional categories important to host cell responses to HCMV infection. These categories included genes involved in transcriptional regulation, oncogenesis, and cell cycle regulation, which were more prevalent in cluster 1, and genes involved in immune system regulation, signal transduction, and cell adhesion, which were more prevalent in cluster 2. Within these categories, we found genes involved in the host response to HCMV infection (mainly in cluster 1), as well as genes targeted by HCMV’s immune evasion strategies (mainly in cluster 2). As the second group of genes identified by the dChip and SVD approach was statistically and biologically significant, our results point out the advantages of using different methods to analyze gene expression data.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Evaluation of the host transcriptional response to human cytomegalovirus infection

Challacombe

Rechtsteiner

Gottardo

et al. 2004

Physiological Genomics

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“…Indeed, integrin molecules, especially ␤1-and ␣ v -integrin subunits, were down-regulated from the surfaces of several, but not all, cell types by Ebola virus GP. Several viruses, including human CMV, down-regulate or bind to integrin subunits and can induce cell rounding and detachment (37). Moreover, similar effects can be induced by antibodies to ␤1-integrin (30).…”

Section: Discussionmentioning

confidence: 99%

Ebola Virus Glycoproteins Induce Global Surface Protein Down-Modulation and Loss of Cell Adherence

Simmons

Wool-Lewis

Baribaud

et al. 2002

J Virol

193

223

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The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293T cells. In this study we provide evidence that GPs from the other pathogenic subtypes, Sudan and Côte d'Ivoire, as well as from Reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at lower levels than Zaire GP. Sequential removal of regions of potential O-linked glycosylation at the C terminus of GP1 led to a step-wise reduction in cell detachment without obviously affecting GP function, suggesting that such modifications are involved in inducing the detachment phenotype. While causing cell rounding and detachment in 293T cells, Ebola virus GP did not cause an increase in cell death. Indeed, following transient expression of GP, cells were able to readhere and continue to divide. Also, the rounding effect was not limited to 293T cells. Replication-deficient adenovirus vectors expressing Ebola virus GP induced the loss of cell adhesion in a range of cell lines and primary cell types, including those with proposed relevance to Ebola virus infection in vivo, such as endothelial cells and macrophages. In both transfected 293T and adenovirus-infected Vero cells, a reduction in cell surface expression of adhesion molecules such as integrin ␤1 concurrent with the loss of cell adhesion was observed. A number of other cell surface molecules, however, including major histocompatibility complex class I and the epidermal growth factor receptor, were also down-modulated, suggesting a global mechanism for surface molecule down-regulation.

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“…The ␣2␤1, ␣V␤3, and ␣6␤1 integrins are important human cytomegalovirus receptors (23). Human cytomegalovirus infection has been shown to down-regulate ␣2␤1 and ␣5␤1 but upregulate ␣6␤1 on endothelial cells, down-regulate ␣1␤1 on fibroblasts, and up-regulate ␤1 integrins on monocytes and prostate tumor cells to facilitate motility (8,60,63,68). Nonpathogenic and pathogenic hantaviruses use ␤1 and ␤3 integrins, respectively, for endothelial cell entry.…”

mentioning

confidence: 99%

Rotavirus Replication in Intestinal Cells Differentially Regulates Integrin Expression by a Phosphatidylinositol 3-Kinase-Dependent Pathway, Resulting in Increased Cell Adhesion and Virus Yield

Halász

Holloway

Turner

et al. 2008

J Virol

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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 ␣2␤1 and ␤2 integrins was up-regulated, whereas that of ␣V␤3, ␣V␤5, and ␣5␤1 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 ␣2␤1 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.Rotavirus is a major cause of dehydrating gastroenteritis in infant humans and animals throughout the world. Differentiated epithelial cells on villi in the small intestine (enterocytes) are the main targets of infection, leading to cell death, a reduction in villus epithelium area, loss of absorptive capacity, and osmotic dysregulation (3,7,48,53). Enterocytes are attached to the basement membrane through interactions between the basement matrix and cell-surface adhesion molecules, mainly members of the integrin family (4,6,49,64). Increased enterocyte loss is a feature of rotavirus disease, suggesting that reduced enterocyte adhesion occurs (9). However, the molecules involved in changes in attachment of enterocytes to the matrix during rotavirus infection and how this process relates to viral replication and pathogenesis have not been analyzed.Integrins provide a means for cells to respond to their environment through intracellular signaling networks controlling crucial cellular processes such as adhesion, proliferation, migration, differentiation, and survival (1,20,38,55,69). These ␣␤ heterodimeric glycoproteins have been identified as cellular receptors or entry cofactors for many viruses, including rotavi...

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Alteration in the expression of endothelial cell integrin receptors α5β1 and α2β1 and α6β1 after in vitro infection with a clinical isolate of human cytomegalovirus

Cited by 26 publications

References 19 publications

Evaluation of the host transcriptional response to human cytomegalovirus infection

Evaluation of the host transcriptional response to human cytomegalovirus infection

Ebola Virus Glycoproteins Induce Global Surface Protein Down-Modulation and Loss of Cell Adherence

Rotavirus Replication in Intestinal Cells Differentially Regulates Integrin Expression by a Phosphatidylinositol 3-Kinase-Dependent Pathway, Resulting in Increased Cell Adhesion and Virus Yield

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