Herpesvirus quiescence in neuronal cells: Antiviral conditions not required to establish and maintain HSV-2 quiescence

We previously described a novel in vitro model of a non-productive herpes s implex virus type 1 (HSV-1) infection in neurally differentiated (ND)-PC12 cells that allows for inducible virus replication upon forskolin and heat s tress (HS) treatment. In this research, we further characterized the model with respect to HSV-2 strain 333. We found that: (i) ND-PC12 cells are non- permissive to HSV-2 replication; (ii) HSV-2 can establish a quiescent infec tion, like HSV-1, in ND-PC12 cells with the transient use of acycloguanosin e (ACV); however unlike HSV-1, anti-viral conditions are not obligatory to establish and maintain a quiescent state; (iii) the quiescent state is main tained in the presence of Vero cell cocultivation indicating that such cult ures are free of infectious virus; and (iv) a high percentage of quiescentl y infected (QIF)-PC12 cell cultures (80-100%) produce HSV-2 in response to forskolin and HS (43 degrees C, 3 h) treatment for as long as 4 weeks post infection. These findings indicate that ND-PC12 cells can harbor HSV-2 in a cryptic and non-productive state that is reversible. This model has appeal ing features for studying gene expression during the establishment, mainten ance and reactivation phases of the HSV-2 quiescent state in cell culture.