Cytomegalovirus infection decreases expression of thrombospondin-1 and-2 in cultured human retinal glial cells: Effects of antiviral agents

In fibroblasts, infection with human cytomegalovirus (HCMV) inhibits expres sion of the extracellular matrix proteins thrombospondin-1 and -2 (TSP-1 an d TSP-2). These effects may depend on expression of HCMV immediate-early (I E) genes, which are activated by cellular transcription factor NF-kappa B. The influence of HCMV infection on TSP-I and TSP-2 expression and the abili ty of different antiviral drugs to prevent these cellular changes in permis sive cultures of human retinal glial cells were observed. Ganciclovir inhib ited only HCMV late antigen (LA) expression, whereas antisense oligonucleot ide ISIS 2922 and peptide SN50, inhibitors of HCMV IE expression and NF-kap pa B activity, respectively, inhibited both IE and LA expression. ISIS 2922 and SN50, but not ganciclovir, prevented down-modulation of TSP-1 and TSP- 2. The results showed that HCMV-induced down-modulation of TSP-1 and TSP-2 in retinal glial cells is prevented by inhibition of HCMV IE expression. Th ese findings may be relevant to pathogenesis and treatment of HCMV retiniti s.