Interaction between cyclic nucleotides and herpes simplex viruses: productive infection.

Infection of human fibroblasts and HEp-2 cells with herpes simplex virus type 1 (HSV-1) produced a decrease in the intracellular levels of cyclic adenosine 5'- monophosphate (cAMP) and a concomitant increase in the cyclic guanosine 5'- monophosphate (cGMP) levels. In both cell cultures, changes in cyclic nucleotide levels were first observed at 6 h after viral inoculation and were maximal at 12 h. In human fibroblasts, the addition of theophylline, dibutyryl cAMP, or papaverine (cAMP-enhancing compounds) decreased significantly the yield of HSV-1, whereas the addition of insulin or dibutyryl cGMP (cGMP-enhancing compounds) increased the viral yield. In HEp-2 cells, only theophylline decreased the yield of HSV-1, and the cGMP-enhancing compounds had no apparent effect. Cyclic nucleotide enhancing compounds exhibited their effect only if added to either cell culture within the first 3 h after inoculation with HSV-1.