The interferon-inducible 204 gene is transcriptionally activated by mouse cytomegalovirus and is required for its replication

Infection of cells with viable or UV-Inactivated murine cytomegalovirus (MC MV) increased the IFN-inducible 204 gene at both the mRNA and the protein l evels. The activity of a reporter gene driven by the mouse Ifi204 promoter induced following virus infection showed that this increase was due to tran scriptional activation, Moreover, FACS analysis of infected mouse embryo fi broblasts (MEF) stably transfected with a p204-dominant-negative mutant (p2 04dmMEF) revealed that they do not accumulate at the G1/S border in the sam e way as infected MEF transfected with the empty vector (neoMEF). MCMV DNA synthesis is significantly delayed (144 h in p204dmMEF vs 72 h in neoMEF), due to retarded expression of viral genes, namely, IE1 and DNA polymerase, as shown by Western blot comparison of p204dmMEF and neoMEF extracts. These results demonstrate that MCMV may exploit the Ifi204 gene to regulate the cell cycle and enhance Its DNA synthesis. (C) 2001 Academic Press.