Herpes simplex virus type 2 (HSV-2) genes expressed in neuronal cells in response to stress stimuli that trigger latency reactivation are largely unknown. Using a chloramphenicol acetyltransferase (CAT) reporter assay we found that stress caused a significant (P < .001) increase in ICP10 expression in neuronal cells. Up-regulation correlated with activator protein (AP)-1 activation, notably c-Jun and c-Fos that bind cognate elements in the ICP10 promoter. It was blocked by mutation of the AP-1 motifs in the ICP10 promoter. ICP10 expression protected neuronal cells from stress-induced apoptosis. The data suggest that ICP10 may contribute to HSV-2 reactivation by increasing neuronal survival.