Herpes simplex virus gene expression in neurons: Viral DNA synthesis is a critical regulatory event in the branch point between the lytic and latent pathways

Herpes simplex virus establishes a latent infection in peripheral neurons. We examined viral gene expression in rat peripheral neurons in vitro and determined that viral gene expression is attenuated and delayed in these neurons compared with that in Vero cells. In addition, using pharmacologic and genetic blocks to viral DNA synthesis, we found that viral alpha and beta gene expression was upregulated by viral DNA synthesis. Although maximal gene expression in neurons requires viral DNA synthetic activity, activation of viral gene expression was seen even in the presence of herpes simplex virus DNA polymerase inhibitors, but not in the absence of the origin binding protein. Initiation of viral DNA synthesis is apparently a key regulatory event in the balance between the lytic and latent pathways in peripheral neurons.