MacCormac, Luci P.; (1998) The effect of cytomegalovirus infection of endothelial cells on cell surface molecules involved in leukocyte adhesion, migration and immune recognition. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

CMV has been detected in a wide variety of cell types in vivo. Endothelial cell involvement, in particular, is associated with more severe infections, although the reasons are unclear. An in vitro model of virus infection was therefore established, in order to test the effect of CMV infection on endothelial cells. Using this model, a difference in the ability of laboratory strains and clinical isolates of CMV to infect endothelial cells was determined. The laboratory strains only produced a limited infection in a proportion of the cells, despite the induction of virus replication by the short chain fatty acid, sodium butyrate. In contrast, two recent clinical CMV isolates showed continuous infection of endothelial cells in the absence of prior stimulation of the cells. Moreover, the clinical strains were able to spread to surrounding uninfected cells, whereas the laboratory strains were not. Following infection of endothelial cells with the CMV strains mentioned above, it was found that the expression of a number of cell surface molecules were altered. Thus, all virus strains increased the expression of ICAM-1, but decreased the expression of PECAM-1, ICAM-2, and MHC Class I. Furthermore, the ability of CMV-infected endothelial cells to induce the molecules E-selectin and MHC Class II, in response to cytokine stimulation, was abolished. However, a difference in the ability of the virus strains to increase the expression of LFA-3 was observed. This was not cell-type specific, as a similar phenomenon occurred when the more permissive fibroblast cell type was used. In addition, novel Fc?R were also induced on the CMV- infected endothelial cells. All the effects described above were not due to the secretion of soluble factors during the course of the infection. Finally, CMV infection altered the ability of leukocytes to adhere to, and transmigrate through unactivated or cytokine-activated endothelial cell monolayers. This was partly due to the secretion of soluble factors. Thus, CMV infection of endothelial cells resulted in changes to cell surface molecule expression, and to leukocyte recruitment, which might alter the ability of the host's immune system to respond to the infection.

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