Human cytomegalovirus infection downregulates the expression of glial fibrillary acidic protein in human glioblastoma U373MG cells: identification of viral genes and protein domains involved

Human cytomegalovirus (HCMV) has tropism for glial cells, among many other cell types. It was reported previously that the stable expression of HCMV immediate-early protein 1 (IE1) could dramatically reduce the RNA level of glial fibrillary acidic protein (GFAP), an astroglial cell-specific intermediate filament protein, which is progressively lost with an increase in glioma malignancy. To understand this phenomenon in the context of virus infection, a human glioblastoma cell line, U373MG, was infected with HCMV (strain AD169 or Towne). The RNA level of GFAP was reduced by more than 10-fold at an m.o.i. of 3 at 48 h post-infection, whilst virus treated with neutralizing antibody C23 or with UV light had a much-reduced effect. Treatment of infected cells with ganciclovir did not prevent HCMV-mediated downregulation of GFAP. Although the expression of GFAP RNA is downregulated in IE1-expressing cells, a mutant HCMV strain lacking IE1 still suppressed GFAP, indicating that other IE proteins may be involved. IE2 is also proposed to be involved in GFAP downregulation, as an adenoviral vector expressing IE2 could also reduce the RNA level of GFAP. Data from the mutational analysis indicated that HCMV infection might affect the expression of this structural protein significantly, primarily through the C-terminal acidic region of the IE1 protein.