Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: Viral block to the accumulation of antiviral mRNAs

The effect of human cytomegalovirus (HCMV) infection on cellular mRNA accum ulation was analyzed by gene chip technology. During a 48-h time course aft er infection of human diploid fibroblasts, 1,425 cellular mRNAs were found to be up-regulated or down-regulated by threefold or greater in at least tw o consecutive time points. Several classes of genes were prominently affect ed, including interferon response genes, cell cycle regulators, apoptosis r egulators, inflammatory pathway genes, and immune regulators. The number of mRNAs that were up-regulated or down-regulated were roughly equal over the complete time course. However, for the first 8 h after infection, the numb er of up-regulated mRNAs was significantly less than the number of down-reg ulated mRNAs. By analyzing the mRNA expression profile of cells infected in the presence of cycloheximide, it was found that a minimum of 25 mRNAs wer e modulated by HCMV in the absence of protein synthesis. These included mRN As encoded by a small number of interferon-responsive genes, as well as bet a interferon itself, Cellular mRNA levels in cytomegalovirus-infected cells were compared to the levels in cells infected with UV-inactivated virus. T he inactivated virus caused the up-regulation of a much greater number of m RNAs, many of which encoded proteins with antiviral roles, such as interfer on-responsive genes and proinflammatory cytokines. These data argue that on e or more newly synthesized viral gene products block the induction of anti viral pathways that are triggered by HCMV binding and entry.