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Human Cytomegalovirus Infection Downregulates the Expression of Glial Fibrillary Acidic Protein in Human Glioblastoma Cells, U373MG:Identification of Viral Genes and Protein Domains Involved.


Posted on: 03/08/2009

J Gen Virol. 2009 Mar 4. [Epub ahead of print] Related Articles


Human Cytomegalovirus Infection Downregulates the Expression of Glial Fibrillary Acidic Protein in Human Glioblastoma Cells, U373MG:Identification of Viral Genes and Protein Domains Involved.

Koh K, Lee K, Ahn JH, Kim S.

Seoul National University;

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

PMID: 19264642 [PubMed - as supplied by publisher]


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