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 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)-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 appealing features for studying gene expression during the establishment, maintenance and reactivation phases of the HSV-2 quiescent state in cell culture.
Danaher
R J
RJ
Department of Oral Health Practice, University of Kentucky College of Dentistry, Lexington, Kentucky, KY 40536-0297, USA.
Jacob
R J
RJ
Miller
C S
CS
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D005576:Colforsin / Q000494:pharmacology; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D014709:Vero Cells; D010948:Viral Plaque Assay; D014775:Virus Activation; D017735:Virus Latency
D000998:Antiviral Agents; D005576:Colforsin; D000212:Acyclovir