Evidence for the potential influence of cyclic nucleotides on maintenance of or reactivation from latency of herpes simplex virus in trigeminal ganglionic neurons.
Herpes simplex virus infections are epidemic throughout developed countries, and recurrent herpes simplex keratitis is the most common cause of corneal blindness in these countries, NIH (1973). No available antiviral agent is capable of eradicating the state of viral ganglionic latency, and hence no effective treatment currently exists for prevention of viral re-activation from latency, with resultant recurrent infectious viral clinical manifestations. Putative triggers of re-activation include stress, sunburn, menses, trauma, and fever. These 'triggers' seem to share at least one common characteristic: the potential ability to influence intracellular cyclic nucleotide levels through the action of such first order messengers as catacolamines (stress, trauma) and/or arachadonic acid metabolites (sunburn, fever, trauma, and menses). We exploited an in vitro model of HSV ganglionic latency, and developed a model of in vitro organ culture ganglionic viral reactivation from latency. We then examined the effect of a variety of agents on this model. We found that agents which have been shown to elevate cyclic AMP levels consistently produce increased viral shedding (compared to control, spontaneous reactivation rate) in our model of viral reactivation from latency. In contrast, agents which have been shown to depress c-AMP levels and/or to elevate c-GMP levels inhibit viral reactivation from latency in this in vitro model. We conclude that intracellular cyclic nucleotide levels may influence events which control herpes simplex genome transcription.
Foster
C S
CS
Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA.
Opremcak
E M
EM
Tolchin
N
N
D000818:Animals; D002478:Cells, Cultured; D015342:DNA Probes; D004279:DNA, Viral / Q000032:analysis; D005128:Eye Diseases / Q000382:microbiology; D006561:Herpes Simplex / Q000382:microbiology; D007124:Immunoenzyme Techniques; D051379:Mice; D009712:Nucleotides, Cyclic / Q000378:metabolism / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects; D018139:Simplexvirus / Q000254:growth & development*; D012668:Trigeminal Ganglion / Q000382:microbiology*; D014775:Virus Activation / Q000187:drug effects
D015342:DNA Probes; D004279:DNA, Viral; D009712:Nucleotides, Cyclic