Down-regulation of integrin 1/beta1 expression and association with cell rounding in human cytomegalovirus-infected fibroblasts

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Abstract
Human cytomegalovirus (HCMV) causes a c.p.e. characterized by rounding of the infected cell. Since interactions with the extracellular matrix may be involved in the cell rounding, we have analysed the expression of integrins, which are the main cell surface receptors involved in cell-substrate adhesion and spreading. By FACS analysis, a selective decrease in cell surface expression of α1/β1 integrin was observed in HCMV-infected fibroblasts. This decrease coincides with cell rounding. Immunoprecipitation studies and FACS analysis of permeabilized cells have further demonstrated that total levels of this integrin are decreased in infected cells, suggesting that the reduction in cell surface α1/β1 integrin is not due to a defect in transport to the surface. Furthermore, we have ruled out the possibility that the observed decrease in α1/β1 expression is caused by a cytokine released from the infected cells by showing that the reduction is abolished by inactivating the HCMV with u.v. irradiation, and that conditioned medium from HCMV-infected cells has no effect on expression of α1/β1 integrin in uninfected cells. Concomitant with the reduction in α1/β1 levels, the HCMV-infected fibroblasts show a reduced ability to adhere to laminin and collagen IV. Taken together the data indicate that de novo synthesis of HCMV protein(s) causes a decreased assembly/expression of α1/β1 integrin, coincident with the well characterized morphological alterations of the infected cell.

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