Effect of cyclic AMP and cyclic GMP on the activity of interferon against herpes simplex virus types 1 and 2, and vesicular stomatitis virus.

The antiviral action of interferon (IFN) on herpes simplex virus (HSV) types 1 and 2, and vesicular stomatitis virus (VSV) was examined with respect to the intracellular levels of cyclic adenosine monophosphate (CAMP) and cyclic guanosine monophosphate (CGMP) in human fibroblast (HF) cultures. Interferon by itself increased the intracellular levels of CAMP, but had no effect on the CGMP levels. Inoculation of HF with HSV, however, decreased the CAMP levels. Also, HSV inoculation elevated the CGMP levels, but VSV did not alter the CGMP levels. When HSV and IFN were added to the HF cultures in various combinations, HSV inhibited the IFN-induced elevation of CAMP and increased the CGMP levels to that characteristically observed with HSV inoculation in the absence of IFN. In contrast, IFN antagonized the VSV-associated decrease in CAMP levels. Although the yields of VSV were unaltered by the presence of CAMP- or CGMP-enhancing compounds, the yields of HSV were decreased with CAMP enhancers and increased with CGMP enhancers. the combination of IFN and CAMP enhancers had an additive effect in reducing the yields of HSV. Neither the CAMP or CGMP enhancers affected the action of IFN on VSV. These studies suggest that the interactions observed between HSV and cyclic nucleotides might account for the relatively refractive nature of HSV, as compared to VSV, toward the antiviral activity of IFN.