University of Kentucky Research Foundation

Robert J Danaher

Craig Miller

Robert J Jacob

We previously described a novel in vitro model of a non-productive herpes simplex virus type 1 (HSV-1) infection in neurally-differentiated (ND)-PC12 cells that allows for inducible virus replication upon forskolin and heat stress (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 infection, like HSV-1, in ND-PC12 cells with the transient use of acycloguanosine (ACV); however unlike HSV-1, anti-viral conditions are not obligatory to establish and maintain a quiescent state; (iii) the quiescent state is maintained in the presence of Vero cell cocultivation indicating that such cultures are free of infectious virus; and (iv) a high percentage of quiescently infected (QIF)-PC 12 cell cultures (80-100%) produce HSV-2 in response to forskolin and HS (43&deg; 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 appealing features for studying gene expression during the establishment, maintenance and reactivation phases of the HSV-2 quiescent state in cell culture. (2000) 6, 296-302.

Neuronal cell model and methods of use thereof

The present invention provides, inter alia, a PC12 cell quiescently infected with a neurotropic virus. Preferred quiescently-infected neural cells are those wherein the neurotropic virus is a neurotropic herpes virus. Methods related to these and other materials are also provided.

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Lexington, KY, United States of America

Robert J Danaher