Herpes simplex virus type 1 modulates cellular gene expression during quiescent infection of neuronal cells

Gene expression profiling of neuronally-differentiated (ND)-PC12 cells quiescently infected (QIF) with herpes simplex virus type 1 (HSV-1) was performed to determine the response of neuronal cells to long-term maintenance of a non-replicating viral genome independent of the heterogeneous response that occurs in latently infected ganglia. Quiescent infections were characterized by 606 up-regulated and 821 down-regulated cellular genes (P < 0.005) compared to parallel, identically treated, mock-infected cultures. Gene ontology analyses suggested that up-regulated cellular genes were involved in steroid biosynthesis and mitogen-activated protein kinase signaling pathways and significantly overrepresented for transcription factor and transcription regulatory functions. Many of the most up-regulated cellular genes encode for proteolytic enzymes involved in neurite outgrowth/axon remodeling. Genes involved in DNA and nucleotide metabolism and apoptosis tended to be down-regulated. These findings demonstrate that a quiescent HSV-1 infection significantly alters neuronal gene expression in ways that may promote survival of the host cell and maintenance of latency.