MECHANISMS OF HERPES-SIMPLEX VIRUS TYPE-1 REACTIVATION

Primary cultures of trigeminal ganglion (TG) cells from herpes simplex virus type 1 (HSV-1) latently infected mice were used to study reacti vation. Expression of HSV-1 latency-associated transcripts was noted i n TG cell cultures. Infectious virus appeared in 75% of culture supern atants within 120 h after heat stress. Like,vise, HSV-1 lytic-phase mR NA and proteins were detectable 24 h after heat stress. HSV-1 antigen first appeared in neurons after heat stress, indicating the neurons we re the source of reactivation. The effect of heat stress duration on r eactivation was determined. Reactivation occurred in 0, 40, or 67% of cultures after a 1-, 2-, or 3-h heat stress, respectively. However, 72 -kDa heat shock protein expression was induced regardless of heat stre ss duration. Thus, reactivation was not a direct result of inducing th e heat shock response. The capacities of several drugs to induce react ivation were also evaluated. While neither epinephrine, forskolin, nor a membrane-permeable cyclic AMP analog induced reactivation, dexameth asone did so in a dose-dependent manner. Furthermore, dexamethasone pr etreatment enhanced the kinetics of heat stress-induced reactivation f rom TG cells. Collectively, the results indicate that TG cell cultures mimic important aspects of in vivo latency and reactivation. Therefor e, this model may be useful for studying signalling pathways that lead to HSV-1 reactivation.