DOWN-REGULATION OF INTEGRIN ALPHA-1 BETA-1 EXPRESSION AND ASSOCIATIONWITH CELL ROUNDING IN HUMAN CYTOMEGALOVIRUS-INFECTED FIBROBLASTS/

Human cytomegalovirus (HCMV) causes a c.p.e. characterized by rounding of the infected cell. Since interactions with the extracellular matri x may be involved in the cell rounding, we have analysed the expressio n of integrins, which are the main cell surface receptors involved in cell-substrate adhesion and spreading. By FAGS analysis, a selective d ecrease in cell surface expression of alpha 1/beta 1 integrin was obse rved in HCMV-infected fibroblasts. This decrease coincides with cell r ounding. Immunoprecipitation studies and FAGS analysis of permeabilize d cells have further demonstrated that total levels of this integrin a re decreased in infected cells, suggesting that the reduction in cell surface alpha 1/beta 1 integrin is not due to a defect in transport to the surface. Furthermore, we have ruled out the possibility that the observed decrease in alpha 1/beta 1 expression is caused by a cytokine released from the infected cells by showing that the reduction is abo lished by inactivating the HCMV with u.v. irradiation, and that condit ioned medium from HCMV-infected cells has no effect on expression of a lpha 1/beta 1 integrin in uninfected cells. Concomitant with the reduc tion in alpha 1/beta 1 levels, the HCMV-infected fibroblasts show a re duced ability to adhere to laminin and collagen IV. Taken together the data indicate that de novo synthesis of HCMV protein(s) causes a decr eased assembly/expression of alpha 1/beta 1 integrin, coincident with the well characterized morphological alterations of the infected cell.