In order to learn more about the cellular response to viral gene activity during latency and reactivation of herpes simplex virus type 1 (HSV-1), the authors have employed microarray analysis. On an array of about 1200 cellular genes, approximately 56 genes were found to be differentially regulated in infected trigeminal ganglia of mice, compared to uninfected mice, during latency and reactivation. Of these genes, 10 were examined more closely using quantitative real-time polymerase chain reaction (PCR) to confirm the microarray results. Genes involved in interferon and other signaling pathways appeared to predominate in response to a latent or reactivating HSV infection. Interestingly, some genes found to be differentially regulated in latently infected ganglia are neuronal-specific genes (pro-opiomelanocortinin; zinc finger proteins of the cerebellum 1 and 2). During reactivation, the involvement of several cell signaling molecules that may be important for the initiation of an HSV infection was observed, including various receptors and molecules involved in cell-cell spread.