Reactivation of latent herpes simplex virus from dissociated identified dorsal root ganglion cells in culture -- Kennedy et al. 64 (7): 1629 -- Journal of General Virology

This study demonstrates that herpes simplex virus (HSV) types 1 and 2 can reactivate from dissociated cultured dorsal root ganglion (DRG) neurons obtained from latently infected mice. Researchers isolated DRG cells from mice infected 3+ months earlier and cultured them in vitro. Using immunofluorescence with neuron-specific markers and HSV-specific antibodies, they identified that viral antigen expression first appeared in neurons by day 3 after dissociation, with infectious virus released by days 3-5. Approximately 0.4% of neurons released infectious virus. Notably, reactivation occurred even in the presence of neutralizing anti-HSV antibodies, indicating that antibodies are not required for viral reactivation. When uninfected DRG cultures were directly infected with HSV, cytopathic effects appeared primarily in fibroblastic cells rather than neurons, suggesting neurons are relatively resistant to lytic infection. The recovered virus had identical restriction enzyme profiles to the originally inoculated virus, confirming its identity.

Key findings

• HSV reactivates from dissociated cultured DRG neurons as early as 3 days after tissue dissociation, with viral antigen expression first appearing in neurons before infectious virus release
• Approximately 0.4% of neurons support HSV reactivation and release infectious virus, affecting both large and small neurons
• HSV reactivation occurs in the presence of neutralizing antibodies, demonstrating that serum antibodies are not required to maintain or break latency
• Neurons show relative resistance to lytic HSV infection compared to fibroblasts and Schwann cells, suggesting different mechanisms between viral reactivation and de novo infection